For 25 years, the Breslow depth of primary tumors has remained the most accurate prognostic test of survival for primary melanoma. However a number of studies have indicated that outcome for intermediate-thickness melanomas (0.75-2.49 mm) is often at variance with that predicted by the Breslow depth. This study investigated c-myc oncogene expression in 92 primary tumors of intermediate thickness using flow cytometry. Oncoprotein expression was detected in 87 tumors (95%) with a median positivity of 48% (range, 0%-96%). Survival analysis performed using the Kaplan-Meier method revealed a significant association between oncoprotein positivity and clinical outcome (p < 0.01, log-rank test). Multifactorial analysis of survival using Cox's proportional hazards model revealed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including the Breslow depth (chi(2) = 9.68, p< 0.01). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for intermediate-thickness primary melanoma.