This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (</=5 cm in 16) and multinodular/massive in 76. After a median follow-up of 17 months, 79 patients died, the 1-, 2-, and 3-year survival being 54%, 40%, and 28%. The multivariate study identified PST (P =.01), constitutional syndrome (P =.04), vascular invasion (P =.001), and extrahepatic spread (P =.04) as independent predictors for mortality. The 1-, 2-, and 3-year survival for the 48 patients without adverse factors (Stage 0) was 80%, 65%, and 50%, respectively, and 29%, 16%, and 8% in the 54 patients with at least one adverse parameter (Stage I). Therefore, Stage 0 would correspond to an intermediate stage, while Stage I would represent an advanced status, before reaching an end-stage phase. In conclusion, the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern. Therapeutic trials should be designed and evaluated considering these characteristics.