Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell-stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n = 59) and lesions from patients with a longer survival (n = 285). Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1 +/- 14.1 years versus 58.8 +/- 15.3 years), had developed earlier after the primary tumor (mean time of 21.7 +/- 19.9 months versus 43.3 +/- 27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p < 0.001) and PRECOLL (82.8% versus 57.6; p < 0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p < 0.01) and PREFAT (68.1% versus 46.8%; p < 0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen. In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.