The patient with metastatic adeno- or undifferentiated carcinoma who presents with a cryptic primary is subjected to an extensive diagnostic search. These efforts apparently stem from the following assumptions: 1). The ultimately proven primary sites in such patients will occur with the same frequency as the most commonly occurring carcinomas (i.e., lung, breast, colon, prostate, etc.); and 2). Metastatic patterns and histologies seen at diagnosis are the same as for patients presenting with these more common tumors. Our data contradict these assumptions. For example, the most commonly occurring unknown primary was pancreas. Rarely occurring primaries included breast and prostate. Lung cancer was observed frequently, but the presentation was atypical because of the large proportion of female patients. In addition, the metastatic patterns at diagnosis were unusual for many of the ultimately proven primary sites. In an attempt to deal with these contradictions, a method to search for new relationships between primary site and metastatic-histologic presentations was employed. This method succeeded in placing the location of the primary cancer to above or below the diaphragm in 80% of the patients studied retrospectively. Tested prospectively in a small group of patients, the method appears to be clincally useful. Finally, in this study we have made the diagnosis, antemortem, of the primary cancer site (PCS) in only 30 of 264 patients. The failure to find the primary site, dispite extensive radiologic work-up, was disappointing to the authors, and emphasizes the difficulty of finding PCS antemortem. In our study pancreas and lung appear to be most common cryptic primary sites.