The diversity of melanoma patterns greatly impairs the interpretation of malignant cells in effusion samples. The presence of melanin pigments greatly helps determine the histogenetic origin of the tumor, but unfortunately many cases do not exhibit this feature. We reviewed cases with a definitive diagnosis of melanoma in order to identify some useful characteristics of the morphologic examination of effusions. We also subjected the effusions to the HMB45 immunoreaction to determine the diagnostic usefulness of this monoclonal antibody. The study was performed on 21 effusion samples containing malignant cells, and the main cytologic findings were similar to those on other neoplasms except for the presence of melanin pigment. The HMB45 immunoreaction was very sensitive, confirming the diagnosis in 14 of 18 cases (77.8%). Melanin pigments seem to be useful markers for melanoma in effusions, and HMB45 can be used as an ancillary method in the differential diagnosis.