The spectrum of so-called space-occupying small (0.5-2.5 cm) sizable nodules arising in the cirrhotic liver includes a series of hyperplastic (large regenerative), dysplastic (low- and high-grade dysplastic), and malignant hepatocellular (well-differentiated hepatocellular carcinoma, HCC) nodules. Major progress in their classification and understanding was achieved through image analysis techniques and careful histological dissection of explanted native livers. Needless to say, the actual understanding of their natural history is crucial to a proper histological classification. The differential diagnosis of these hepatocellular nodules is difficult, particularly on biopsy specimens of focal liver lesions revealed by ultrasound (US), taken during the follow-up of cirrhotic patients. In this study we attempted to summarize, on the basis of our experience, essential clinicopathological features useful to distinguish the different nodules on needle biopsy. Synoptic tables of differential diagnosis and figures of elementar lesions, which have to be looked for, are provided. Only the continuous integration of clinical features, image analysis information of pathological findings, and follow-up data allows establishing the autonomy of these polymorphic and controversial entities and the boundaries between them.