The spontaneous regression of HCC is extremely rare. This event could be explained by a strong and persistent activation of the immune system directed against the neoplastic cells or a sudden change in vascular inflow resulting in autoinfarction. We report herein a case of 51-year-old man who presented with a diagnosis of HCV induced cirrhosis. The initial liver ultrasound revealed an ill defined right lobe lesion approximately 7 x 8 cm in diameter, involving segments VII and VIII with malignant portal vein thrombosis. Baseline laboratory tests included: FBS 72 mg/dl, 2-hour postprandial sugar was 166 mg/dl, Hb 12.1 g/dl, WBC 3 000/cmm, neutrophils 1500/cmm, platelet count 70 000/cmm, ALT 85 U/L, AST 100 U/L, total serum bilirubin 1.8 mg/dl, serum albumin 3.3 g/dl, prothrombin time 13.1 seconds (70%) with calculated Child A compensated cirrhosis according to Child Pugh scoring. The initial AFP was 19,309 ng/ml. The triphasic CT (Figure 1) revealed a large invasive right lobe mass in segment IV,V,VI,VIII with an arterial blush and rapid washout pattern diagnostic for HCC, with associated with thrombosis of the right branch of portal vein with a porta hepatis lymphe node consistent with metastatic HCC. The patient had an ECOG performance status of 0, and according to the BCLC staging for HCC, Stage C (advanced stage) disease. Sorafenib was not available and the patient did not receive any other treatment. A triphasic CT, performed 4 months later, demonstrated (Figure 2) a marked decrease in the size of the lesion, with 4 x 3.8 cm in maximum dimensions. The thrombosed right portal vein branch showed cavernous transformation and no malignant neovascularization. The AFP was 1,923 ng/ml, laboratory tests: FBS 206 mg/dl, urea 22 mg/dl, creatinine 0.7 mg/dl, ALT 63 U/L, AST 77 U/L, total serum Bilirubin was 1.7 mg/dl, serum albumin 3.3g/dl. The patient was at a good general condition and remained at an ECOG performance status of 0. In conclusion, we report here a rare event in a patient with HCC, wherein the HCC underwent a spontaneous event that resulted in a marked decrease in the tumor size and area of neovascularization. This rare spontaneous event, which can change a patient's prognosis substantially, needs to be recognized by clinicians who monitor patients with HCC, both on and off treatment as well as in clinical trials.Figure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)