Ninety five patients who developed in transit melanoma either as their initial site of recurrent melanoma or following regional node metastases were retrospectively reviewed. In transit melanoma occurred most frequently on the lower extremity and appeared to be associated with deeply invasive primary tumors. The median time to development of in transit melanoma was 16 months. Eighty-two (86%) of these patients have progressed to systemic disease from 2 to 244 months (median 16 months) following the development of in transit melanoma, and 72 (79%) died (median survival 19 months). Survival appears to correlate with the extent of in transit melanoma and with the disease-free interval. These findings suggest that in transit melanoma represents an early manifestation of systemic disease, warranting careful clinical follow-up and perhaps systemic treatment, when effective therapy becomes available. However, some patients will respond to local immunotherapy, surgical excision, and isolated limb perfusion and will enjoy significant length and quality of life. This sequential approach remains the treatment of choice for this manifestation of metastatic melanoma.