Due to the improved sensitivity of imaging tests, nodular lesions are frequently detected, whether in hepatocellular carcinoma (HCC) screening programs or in other contexts. These tumors usually occur in cirrhotic patients but their identification is as difficult as it is important. Several studies support the idea that the purely morphological concept of small HCC encompasses clinically distinct entities with different prognoses: early HCC, true hepatic carcinoma in situ, and small HCC, fully developed neoplasm with poorer prognosis and response to radical therapy. The distinction between these and other benign nodular lesions such as dysplastic nodules and regeneration nodules is extremely difficult, if not impossible, in lesions of less than 1 cm, even when invasive methods are used. However, the distinction is highly precise for many lesions of more than 2 cm, when only the most up-to-date imaging techniques are employed. Between these two extremes, imaging techniques, together with the use of biomarkers and molecular techniques, provide important information which, nevertheless, rarely avoids uncertainty and which should be critically evaluated to make appropriate decisions according to the specific features of each individual patient.