Acral lentiginous melanoma is a particularly aggressive tumour with a worse prognosis than other varieties of primary cutaneous melanoma. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 45 patients using flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis with stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (Log-Rank test, chi 2 = 16.7, P < 0.0001) and overall survival (Log-Rank test, chi 2 = 8.9, P = 0.002) in tumours with high oncoprotein levels. Multivariate analysis revealed c-myc oncogene expression to be more accurate in predicting clinical outcome than all existing clinicopathological parameters including the Breslow depth (Cox's proportional hazards model, P = 0.0011). This study provides biological evidence to explain the aggressive behaviour of acral melanoma and supports the application of oncogene measurement as an accurate prognostic marker.