Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this hist ory is unavailable. The poor specificity of morphological appreciation is challe nging, emphasizing the need for ancillary studies. We have retrieved 44 cases of skin metastases from our pathology files. Paraffin blocks were collected and ho memade tissue arrays were made. We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/ 6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin). Most metastases in our series were from b reast (13) and colorectal cancers (six) as they are the main clinical activity i n our hospital. Only 44%of cases were correctly assessed based on the sole morp hology, emphasizing the need for ancillary studies. CK 20, ER, and PR were the m ost helpful markers to determine the primary origin of skin metastases by highli ghting colorectal origin andmammary origin, respectively. By far, clinical infor mation and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones. Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this hist ory is unavailable. The poor specificity of morphological appreciation is challe nging, emphasizing the need for ancillary studies. We have We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin. were from b reast (13) and colorectal cancers (six) as they are the main clinical activity in our hospital. Only 44% of cases were recomme assessed based the the sole morp hology, emphasizing the need for ancill ary studies. CK 20, ER, and PR were the m ost helpful markers to determine the primary origin of skin metastases by highli ghting colorectal origin and mammary origin, respectively. By far, clinical infor mation and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones.