We describe a new phenotype of wide occurrence in human cancer: expression of coarse vesicles rich in beta1,6-branched oligosaccharides. beta1,6-branching, catalyzed by GNT-V, is associated with metastasis and predicts poor survival in primary human breast and colon carcinomas. Yet little is known on the histopathology of this phenomenon. We studied beta1,6-branching [determined by leukocytic phytohemagglutinin (LPHA) lectin-histochemistry] in 119 archival specimens of human melanomas and other neoplasms, including carcinomas of the lung, colon, breast, ovary, prostate, kidney, and Hodgkin's lymphoma. At least portions of most tumors (96%) stained to some extent with LPHA. Staining was always, but not exclusively, associated with coarse vesicles. In melanomas, LPHA staining colocalized with CD63 and gp100. In pigmented melanomas, the vesicles were melanized and are known as "coarse melanin." LPHA-positive, coarse melanin was a feature of both tumor cells and melanophages and accounted for the well-known hypermelanotic regions of primary melanomas. LPHA-positive tumor cells varied widely in primaries (melanoma and others), ranging from 0 to 100% for a given tumor, whereas metastases were far more homogeneous (P = 0.0080), with vesicular, LPHA-positive tumor cells comprising >75% of 15 of 16 metastatic melanomas and renal cell carcinomas. In studies by others, GNT-V elicited formation of autophagy-dependent, LPHA-positive vesicles in mink lung alveolar cells (Hariri et al., Mol. Biol. Cell, 11: 255-268, 2000), suggesting that the coarse vesicles in tumors reported here may have been induced by GNT-V. Expression of the phenotype was so common and pervasive that it appeared to be an integral component of the biology of tumor progression. The origin of this phenotype and its biological significance are as yet unclear and will require considerable further study.