The PTEN gene is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Inactivating mutations and deletions of the PTEN gene are found in many types of cancers, including melanoma. However, the exact frequency of PTEN alteration in melanoma is unknown. In this study, we comprehensively reviewed 16 studies on PTEN genetic changes in melanoma cell lines and tumor biopsies. To date, 76 PTEN alterations have been reported in melanoma cell lines and 38 PTEN alterations in melanoma biopsies. The rate of PTEN alterations in melanoma cell lines, primary melanoma, and metastatic melanoma is 27.6, 7.3, and 15.2%, respectively. Three mutations were found in both melanoma cell lines and biopsies. These mutations are scattered throughout the gene, with the exception of exon 9. A mutational hot spot is found in exon 5, which encodes the phosphatase activity domain. Evidence is also presented to suggest that numerous homozygous deletions and missense variants exist in the PTEN transcript. Studying PTEN functions and implications of its mutations and other genes could provide insights into the precise nature of PTEN function in melanoma and additional targets for new therapeutic approaches.