Background: P53 tumor suppressor gene mutation is one of the most common genetic alterations in human malignancies. The mutated from of the gene is stable and can be detected with immunohistochemistry methods. There is much controversy about the expression rate of this gene in malignant melanoma. Objective: To determine the frequency of the P53 antigen expression by sex, age, type and thickness of melanoma, and site of the antigen expression. Patients and methods: Paraffin embedded blocks of 50 patients (45 primary and 5 metastatic) with documented diagnosis of melanoma were deparaffinized and immunostained with D0-7 monoclonal antibody. The lesions were divided depending on the degree of the staining as follows: 1) (No staining), 2) Mild (Less than 10%), 3) Moderate (10%-50%), 4) Severe (More than 50%). Results: Of 50 cases, 27 (54%) evaluated skin biopsy specimens belonged to female patients and 23 (46%) skin biopsies were related to male patients. 40% of lesions were graded as no staining. 36% of lesions showed mild staining, 14% moderate and 10% severe staining. Site of expression was exclusively in the cytoplasm. There was no meaningful statistical relationship between severity of staining and the age group, and sex of the patients, type and thickness of melanoma (P>0.05). Conclusion: Mutation in P53 tumor suppressor gene probably occurs in the early stages of melanoma.