Malignant melanoma (MM) cells do not require all exogenous growth factors of normal melanocytes. It is hypothesized that they make their own growth factors including melanoma growth stimulatory activity (MGSA). Cultured melanoma cells respond to MGSA with increased growth and angiogenesis suggesting a role for MGSA in MM proliferation, differentiation, and progression. We assessed the prognostic significance of MGSA expression in 37 primary MM immunostained for MGSA. Immunostains were graded for intensity (0-3+), percentage of cells immunostained, and location of immunostain (intraepidermal, junctional, or dermal). In addition, 31 melanocytic and 23 dysplastic nevi were similarly studied for MGSA expression. All MM showed the presence of immunostain, 6 (16%) 1+, 12 (32%) 2+, and 19 (51%) 3+. Six (16%) had immunostain in < or = 50% tumor cells, 31 (84%) in >50%. A significant number of MM showed >50% tumor cells staining at the dermal-epidermal junction compared with intraepidermal staining (P <.0001). Intensity and amount of immunostain did not correlate with Clark's or Breslow's level. During a mean follow-up of 60 months (range: 5-101) on 27 patients, there were 4 local recurrences, 6 distant metastases, and 10 deaths. MGSA expression was not of prognostic significance with regard to survival (overall, disease free), or local recurrence or distant metastasis in primary MM. MGSA expression was similar in benign melanocytic and dysplastic nevi. Strong diffuse expression was noted in the junctional component of all junctional and most compound nevi. The dermal component consistently expressed less or no (in 45% of intradermal nevi) MGSA. MGSA expression does not correlate with prognosis in MM. Increased expression of MGSA at the dermal-epidermal junction in nevi and MM may indicate a role for MGSA in early local growth, before development of atypia.