Recent studies have suggested that the appearance of solitary new lesions after a curative resection of hepatocellular carcinoma (HCC) may be closely related to the metachronous multicentric development of HCC. It is therefore extremely important to investigate the histological characteristics of solitary new nodular lesions confirmed to be HCC by an ultrasound (US)-guided needle biopsy. Thirty-five patients with small HCC, < or = 3 cm in diameter, who underwent a curative hepatic resection between 1987 and 1992, were observed for possible recurrence over a period of > or = 1 year. Solitary new lesions confirmed to be HCC were noted in 7 (20.0%) out of 35 cases 10-65 months after operation. All solitary new lesions underwent US-guided needle biopsy, and a histological examination of the biopsy specimen was performed. All seven solitary new lesions were then classified into the following two groups according to the histologic differentiation of biopsy specimens and were found to consist of five well-differentiated HCCs (71.4%) and two moderately differentiated HCCs (28.6%). Three of the five well-differentiated HCCs were accompanied by varying degrees of fatty changes. These morphologic observations suggest that approximately 70% of the solitary new lesions confirmed to be HCC after a curative resection of small HCC may thus be related to the metachronous multicentric origin of HCC. However, it is difficult to estimate the exact incidence of such cases. As a result, curative treatment may sometimes be feasible, even when treating solitary new lesions after resection of HCC. Therefore, we can better evaluate such solitary new nodular lesions after a resection of HCC by means of a histologic evaluation using US-guided needle biopsy.