Patients with unknown primary site cancer represents 5% to 10% of all neoplasia patients. Liver is a favourite site for gastrointestinal tumors, but not only. The adenocarcinomas represents 60% of patients from this group. A detailed physical examination, extensive laboratory and imaging procedures are necessary to locate the primary tumor. However, liver biopsy could be essential for histological diagnosis and important to identify the tumors who may benefit from specific and effective therapy (breast cancer, prostate cancer, ovarian cancer and small-cell carcinoma of the lung). Systemic chemotherapy represents the most frequently treatment, but only patients with good performance status and without co-morbidities may benefit. "Best supporting care" may be the optimal treatment for most patients, majority with poor performance status at the time of diagnosis.