Hepatocellular carcinoma is the fifth most common malignant neoplasm worldwide. Most patients are not candidates to surgical treatment. The prognosis of this neoplasm is poor, with an overall survival rate of 8 weeks in unresectable tumors. Estrogen receptors have been found in up to 33% of this tumors, reason why treatment with tamoxifen or progesterone compounds have been tried to diminish this neoplasm's progression but its use remains controversial. In our institution, thirteen patients were treated with tamoxifen (20- 40 mg/day) and 26 received supportive measures only. The clinical and tumoral characteristics were similar in both groups. Survival in the Tamoxifen group was of 5.5 +/- 1.7 months while in the supportive measures group was of 2.1 +/- 0.5 months (p = 0.018). Other factors related to an increased survival were: female gender and the Okuda score; age, TNM and alphaFP were not related to survival. The multivariate analysis showed that treatment with tamoxifen duplicates survival independently of the tumoral stage and functional hepatic reserve. It seems that the benefit of treatment with tamoxifen is limited and is not associated to the presence of estrogen receptors. In our study a 69 year-old man with diagnosis of non-resectable hepatocellular carcinoma and negative estrogen receptors, was treated with tamoxifen with a partial response and an overall survival of 4 years until November 2005. Despite some case reports that have shown tumoral regression, while other studies do not report any survival benefits. It is important to identify patients that would benefit from treatment with tamoxifen.