BACKGROUND: Sarcoid-like reaction (SLR) is a histological pattern of granulomatous inflammation that is clinically differentiated from sarcoidosis. Since SLR is known to occur in several neoplasias and occasionally causes lymphadenopathy and mimics metastatic malignancy, it needs to be considered whether lymphadenopathy is due to metastasis or SLR for the choice of cancer treatment. Few cases of hepatocellular carcinoma (HCC) with SLR have been reported. Here, a case of HCC with lymphadenopathy diagnosed as SLR without metastasis is presented. CASE PRESENTATION: A 69-year-old woman was admitted to our hospital because of upper abdominal pain. She tested positive for hepatitis C virus ribonucleic acid. Imaging modalities showed an 81 × 65-mm-sized tumor with multiple nodules in segment 3 and a 17 × 12-mm-sized tumor in segment 5 with a common HCC enhancement pattern. In addition, a lymph node in the hepatoduodenal ligament was enlarged at 13 mm in size, suggesting the metastasis of HCC. Hepatectomy of the lateral segment and segment 5 and lymph node dissection in the hepatoduodenal ligament were performed. Both tumors in segments 3 and 5 were pathologically diagnosed as HCC without vessel invasion. The tumors contained necrotic cells and epithelioid cell granulomas with multinucleated giant cells, which is typically observed in sarcoidosis. The dissected lymph nodes also contained epithelioid cell granulomas, as well as giant cells with asteroid bodies. There was no malignancy in the lymph nodes. The pathological findings suggested the coexistence of malignancy and sarcoidosis. However, since the patient did not show any typical findings of pulmonary or cardiac sarcoidosis, the case was diagnosed as HCC with SLR in the primary lesion and regional lymph nodes. CONCLUSIONS: SLR needs to be considered in the differential diagnosis when a cancer patient develops lymphadenopathy. However, lymphadenopathy due to SLR is indistinguishable from that due to metastasis even when using multiple imaging modalities. Pathological examinations may be helpful for the diagnosis.