BACKGROUND: Deregulation of apoptotic pathways in malignant cutaneous melanoma seems to be correlated with chemo resistance and poor prognosis. Furthermore, telomerase (especially h TERT) expression represents a potential target for vaccination regarding some types of malignancies. MATERIALS AND METHODS: Using tissue microarray technology, twenty-five (n=25) paraffin embedded tissue samples of histologically confirmed malignant melanomas were cored at a diameter of 2mm and re-embedded into one final recipient block. Immunohistochemistry was performed by the use of anti-bcl2, anti-caspase3, anti-caspase8 and anti-h TERT antibodies. Protein expression levels were evaluated using an image analysis system. SPSS (chi square test and interrater kappa) was performed for statistical analysis. RESULTS: High level protein overexpression was observed in 1/24 (4.1%), 1/24 (4.1%), 2/24 (8.2%), and 4/24 (17.4%) cases regarding h TERT, Caspase3, Caspase8 και bcl2. Moderate level was observed in 7/24 (29.1%), 8/24 (32.2%), 5/24 (20.2%), and 8/24(32.2%) cases, respectively, whereas reduced or absent expression demonstrated 16/24 (65%), 15/24 (60.2%), 17/24 (68.5%), and 12/24 (50%) cases, respectively. Statistical significance was assessed correlating age to Caspase3 (p=0.05), Breslow to telomerase (p=0.013), Breslow to bcl2 (p=0.053), Clark to telomerase (p=0.008), Clark to bcl2 (p=0.022), and finally ulceration to telomerase (p=0.007). Regarding the intercorrelations between hTERT, caspase-3, caspase-8 and bcl-2 expression, only two arose at a statistically significant level; hTERT expression was positively associated with bcl-2 expression (Spearman’s rho = 0.508, p=0.022) and caspase-3 was positively associated with caspase-8 expression (Spearman’s rho = 0.430, p=0.036). No other intercorrelations reached statistical significance. CONCLUSIONS: BCL2 and telomerase expression are correlated to critical parameters of malignant melanoma, affecting its biological behavior. Furthermore, down regulation of proteins such as caspase 3/8, which normally induce apoptosis, maybe is associated to resistance of applied chemotherapeutic strategies in this type of malignancy.