Malignant melanomas involving the mucosa are rare and aggressive lesions. Their rarity has made the formulation of staging and treatment protocols very difficult, as most of the available information comes from case reports and small case series. We conducted a retrospective study to analyze the behavior of melanomas of the oral mucosa in patients who were treated at Tata Memorial Hospital in Mumbai, a tertiary care referral center for malignancies and one of the largest cancer centers on the Indian subcontinent. During the 22-year period from January 1986 through December 2007, we found only 13 such cases, which had occurred in 8 men and 5 women, aged 26 to 70 years (mean: 37.5). All patients had been offered surgery with curative intent. Mucosal melanomas have exhibited a greater tendency for distant recurrence than for local treatment failure, which is why adjuvant radiation therapy has not been shown to confer any consistent benefit. In our study, only 3 of the 13 patients (23.1%) remained alive 2 years after diagnosis, despite aggressive treatment. Tumor staging, optimal treatment, and prognostic factors for oral mucosal melanoma are far from clear, and further research is needed. Despite the small number of patients in this study, it still represents one of the largest series of oral mucosal melanoma patients in India.