Background Prognostic factors in malignant melanoma are based on clinical data and morphologic examination. were also determined. Results The median follow-up was 104 months. Tumor thickness, Clark’s level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model. Conclusion In general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that this fractal dimension of the nuclear chromatin texture is a new and promising variable in prognostic models of malignant melanomas. Background Malignant melanoma is usually a highly aggressive neoplasia of the skin with a constant and rapidly increasing incidence in the last decades  Prognostic factors are currently based on clinical data and morphologic examination (including variables such as tumor thickness, mitotic rate, etc.) [1-3], which are reliable and reproducible. Other prognostic markers, however, buy Velcade which are not yet used in daily practice, might add important information and thus improve prognosis, treatment, and survival. Therefore a search for new prognostic factors is usually desirable. For this purpose, traditional or new immunohistochemical markers, gene expression arrays, buy Velcade comparative genomic hybridization and mutational profiling have been applied [1,4-9]. Most of these techniques are sophisticated and expensive, requiring equipped laboratories with a tuned personnel specifically, Complete morphological evaluation from the nuclei in histological or cytological arrangements can give important information on cell physiology and, furthermore, can be of considerable great diagnostic and prognostic importance [10-22]. Physiologic or pathologic changes of the cell accompany changes of the chromatin arrangement [21,22]. In particular, neoplastic growth induces important modifications, not only of the DNA, but also of the composition and distribution of the histone buy Velcade and non-histone nuclear proteins, thus provoking alterations of the distribution of heterochromatin in the nucleus. Nuclear texture features have been studied as prognostic markers in neoplasias [11,21,22]. The resources available in commercial softwares are usually restricted to basic morphometric parameters such as diameter, area and perimeter, which cannot adequately measure texture features of nuclei. An important aspect of texture analysis is the determination of fractality, since this feature characterizes the complexity of a structure not revealed by classical morphometry based on Euclidean geometry. Recent studies have shown the fractal nature of nuclear chromatin and of the surrounding nucleoplasmic space [23-25]. Fractals are self-similar structures, i.e. they exhibit comparable features at different magnifications, in a scale-invariant manner. Previous studies have shown that LAMC1 fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias [21,26-29]. Therefore we have investigated whether the fractal dimension of nuclear chromatin measured in routinely stained histological preparations of melanomas can be of prognostic survival value. Methods Study subjects Patients who had superficial spreading cutaneous melanoma, diagnosed and treated at the Hospital AC Camargo, Center for Cancer Research and Treatment between 1994 and 2000 were examined. The study was approved by the local ethics committee (CONEP – 119149, 13th of December 2006.) Inclusion criteria were: 1. tumor size 1 mm; 2. paraffin blocks available for the construction of the tissue microarray; 3. detailed and complete clinical follow-up for at least 60 months in survivors. and 4. clinical information about the cause of death in non-survivors. All cases had been reviewed based on the process established with the Brazilian Melanoma Group as well as the Brazilian Culture of Pathology with a dermatopathologist (GL). The next histological variables had been evaluated: tumor thickness, Clark’s level and mitotic price (amount of mitoses/mm2). Two primary biopsies had been.