Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. The use of cytokeratins 20 (CK20) and 7 (CK7) was proposed to identify the primary sites in this situation. In this review, the results of 29 studies were summarised and the difficulties of data comparison described. Most tumours retained the CK20 phenotype during metastasis, but lung, non-mucinous ovarian, and gastric adenocarcinomas showed statistically significant differences in CK20 expression in the reported primary and metastatic cases. Ductal breast carcinomas, lung and non-mucinous ovarian adenocarcinomas showed significant differences in CK7 expression when primary and metastatic tumours were compared. CK20 positivity alone indicates metastatic spread of adenocarcinoma in several organs. CK7 negativity is consistent with metastases of adenocarcinomas in the lungs, ovaries, liver or serous membranes. CK20/7 phenotyping of adenocarcinomas is a useful diagnostic tool if based on algorithmic and probabilistic approaches and a detailed database.