Diagnostic and prognostic characteristics of 121 North American patients with hepatocellular carcinoma seen in one metropolitan area over a 6-year period were assessed using multivariate analysis. Presenting symptoms commonly included abdominal pain (53%) or mass (34%), anorexia (31%), and ascites (20%); however, the ability to make an early diagnosis was complicated by a variety of unusual symptoms accounting for 25% of presentations. While cirrhosis (63%) and hepatitis B surface antigen (HBsAg) positivity (52%) were common associated findings, the majority of patients (67%) had no prior diagnosis of liver disease. Despite the vascular nature of these malignancies, percutaneous biopsy procedures performed in 66 patients provided diagnostic material in over 85% of cases with little morbidity. Histologic diagnosis was made by blind percutaneous biopsy (41 done, 83% positive), peritoneoscopy with directed percutaneous biopsy (25 done, 88% positive), laparotomy (42 done, 98% positive), or autopsy (19). Percutaneous hepatic biopsy procedures were associated with no mortality and rare bleeding (three cases). Overall median survival was only 18 weeks; multivariate analysis indicated increased bilirubin or presence of pulmonary metastases adversely influenced outcome. Unexpectedly, patients younger than 45 years of age had a significantly (P < 0.01) greater survival (median, 40 versus 9 weeks) than did older patients with this disease. We conclude: (1) hepatocellular carcinoma can be rapidly and safely diagnosed using percutaneous biopsy procedures; (2) North American patients with hepatocellular carcinoma younger than 45 years of age have a more favorable prognosis.