A 68-year-old Caucasian man with hepatitis C virus- related cirrhosis was admitted to our Unit in February 2010 for a diagnostic evaluation of three centimetric hypoechoic focal liver lesions detected by regular sur- veillance ultrasound. The subsequent computer tomog- raphy(CT) led to a diagnosis of unifocal hepatocellular carcinoma(HCC) in Ⅵ hepatic segment, defined the other two nodules in the Ⅵ and Ⅶ segment as sus- pected metastases, and showed a luminal narrowing with marked segmental circumferential thickening of the hepatic flexure of the colon. Colonoscopy detected an ulcerated, bleeding and stricturing lesion at the hepatic flexure, which was subsequently defined as ad- enocarcinoma with a moderate degree of differentiation at histological examination. Finally, ultrasound-guided liver biopsy of the three focal liver lesions confirmed the diagnosis of HCC for the nodule in the Ⅵ segment, and characterized the other two lesions as metastases from colorectal cancer. The patient underwent laparo- tomic right hemicolectomy with removal of thirty-nine regional lymph nodes(three of them tested positive for metastasis at histological examination), and simulta- neous laparotomic radio-frequency ablation of both nodule of HCC and metastases. The option of adju- vant chemotherapy was excluded because of the post- surgical onset of ascites. Abdomen CT and positron emission tomography/CT scans performed after 1, 6 and 12 mo highlighted a complete response to treat- ments without any radiotracer accumulation. After 18 mo, the patient died due to progressive liver failure. Our experience emphasizes the potential coexistence of two different neoplasms in a cirrhotic liver and the complexity in the proper diagnosis and management of the two tumours. A 68-year-old Caucasian man with hepatitis C virus-related cirrhosis was admitted to our Unit in February 2010 for a diagnostic evaluation of three centimetric hypoechoic focal liver lesions detected by regular sur- veillance ultrasound. The subsequent computer tomog raphy (CT ) led to a diagnosis of unifocal hepatocellular carcinoma (HCC) in Ⅵ hepatic segment, defined the other two nodules in the Ⅵ and Ⅶ segments as sus-pected metastases, and showed a luminal narrowing with marked segmental circumferential thickening of the hepatic flexure of the colon. Colonoscopy detected an ulcerated, bleeding and stricturing lesion at the hepatic flexure, which was defined as ad- enocarcinoma with a moderate degree of differentiation at histological examination. Finally, ultrasound-guided liver biopsy of the three focal liver lesions confirmed the diagnosis of HCC for the nodule in the Ⅵ segment, and characterized the other two lesions as metastases from colorectal cancer. patient underwent laparo- tomic right hemicolectomy with removal of thirty-nine regional lymph nodes (three of them tested positive for metastasis at histological examination), and simulta neous laparotomic radio-frequency ablation of both nodules of HCC and metastases. The option of adju - vant chemotherapy was excluded because of the post-surgical onset of ascites. Abdomen CT and positron emission tomography / CT scans performed after 1, 6 and 12 mo highlighted a complete response to treat- ments without any radiotracer accumulation. After 18 mo, the patient died due to progressive liver failure. Our experience emphasizes the potential coexistence of two different neoplasms in a cirrhotic liver and the complexity in the proper diagnosis and management of the two tumors.