Well-differentiated hepatocellular tumors represent a difficult diagnostic problem in hepatopathology with rising clinical impact. The differential diagnosis mainly includes well-differentiated hepatocellular carcinoma (HCC) and its premalignant precursor lesion, the dysplastic nodule (DN), in addition to multiacinar regenerative nodule as well as hepatocellular adenoma (LCA) and focal nodular hyperplasia (FNH). Optimized diagnosis of these lesions is based on exact histomorphological analysis, a close interdisciplinary cooperation as well as good clinical and anamnestic information. Histopathological differential diagnosis requires the search for specific characteristics and detailed analyses of the subtle cytological differences, the histoarchitecture, and also the surrounding nontumorous liver tissue. Special techniques may be helpful in selected cases but currently are of limited importance.