BACKGROUND: The presence of a hypervascular nodule in a patient with cirrhosis is highly suggestive of a hepatocellular carcinoma. CASE PRESENTATION: A 55 year old man with idiopathic refractory anaemia was addressed for the cure of a recently appeared 3.3 cm hypervascular liver nodule. The nodule was not visible on the resected fresh specimen, but a paler zone was seen after formalin fixation. The surrounding liver was fibrotic (METAVIR score F3) and overloaded with iron. However, the paler zone, thought to be the nodule, had in fact a normal architecture, was less fibrotic, and contained some "portal tract-like structures" (but with arteries only); moreover, this paler area was devoid of iron, contained less glycogen and was characterized by foci of clear hepatocytes. CONCLUSION: In spite of the absence of architectural distortion, and a normal proliferative index, the possibility of premalignancy or malignancy should be considered in this type of hypervascular and hyposiderotic nodule, occurring in the context of an iron overloaded liver.