Patients with melanoma who develop nodal metastatic disease represent a group with heterogeneous clinical outcome. Nodal positivity remains the most accurate prognostic marker for regional melanoma although it fails to predict outcome in a significant number of patients. Recent studies have illustrated the prognostic potential of c-myc oncogene expression in melanoma. The aim of this study was to measure c-myc oncoprotein in a series of regional metastatic specimens from 48 patients, and evaluate its use as a marker of clinical outcome. Oncoprotein expression was detected in 46 (96%) of the tumours with a median positivity of 68% (range 0-98%). Survival analysis revealed a significant association between oncoprotein positivity and survival (Long-Rank test, chi 2 = 15.2, P < 0.001). Multivariate analysis of outcome showed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including nodal positivity (chi 2 = 8.34, P = 0.003). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for regional metastatic melanoma.