The biological significance of mast cells and angiogenesis in canine melanomas is unclear. Eighty canine melanomas (56 malignant and 24 benign), investigated to determine the relationship between mast cell count (MCC), microvessel density (MVD) and clinicopathology, revealed significantly higher MCC and MVD counts in malignant melanomas. Evaluation of the prognostic significance of MCC and MVD in malignant melanomas showed a significant correlation between MCC and MVD both within and at the edges of the tumour. Multivariate analysis indicated that MCC and MVD were independent predictors of survival but the former was a significantly better prognostic marker. Greater numbers of mast cells and microvessels were found in malignant melanomas of poor prognosis. The findings demonstrate a prognostic significance of MCC and MVD in canine melanocytic tumours.