An analysis of prognostic factors in 4000 patients with cutaneous malignant melanoma at the Sydney Melanoma Unit and the University of Alabama in Birmingham has demonstrated that the histological features of the primary melanoma become less predictive of survival the more advanced the disease becomes. Thus, whilst 4 features of primary lesions were independent predictors in localized disease (tumour thickness, ulceration, level of invasion and regression), only one of the stronger ones (ulceration) remained predictive in patients with regional lymph node metastases. Once distant spread was evident, there were no parameters of the primary lesion that predicted survival. Thus, in patients with advanced disease prognosis was dictated by the extent of metastatic involvement: the number of positive lymph nodes in stage II patients and the number and location of metastatic sites in stage III patients.