Fifty patients with HCC associated with hepatic cirrhosis underwent intra-arterial injection of Lipiodol UltraFluid (LUF) during diagnostic DSA of liver parenchyma, 42 of them for a complete chemotherapeutic treatment, 8 for an isolated diagnostic control. LUF is known to be specifically captured by HCC neoplastic tissue, with long-term persistence in the lesion if injected in the arterial hepatic tree; this is not the case with other focal hepatic masses. Therefore LUF opacification can be used to demonstrate small daughter tumors not shown by CT or US in cases with evidence of HCC, or to diagnosis HCC in clinically positive patients with no evidence of tumor at non-invasive screening. In our series of patients, accumulation of LUF in the HCC was observed in 100% of the cases, with no false negatives. Two false positives (4%) were observed, due to CT being performed too early (it should be performed not sooner than 10 days after the injection). Overall DSA accuracy was 78%, with 22% false negatives. In 14% of the cases DSA was positive for HCC in patients with aspecific noninvasive screening. CT, performed 10 days after LUF injection, demonstrated HCC daughter tumors not depicted by US, conventional CT, and angiography, in 34% of the cases, and in 9% of the patients only CT/LUF was able to show HCC in clinically positive cases with no evidence of tumor on other imaging techniques. Specificity, sensitivity and over-all accuracy were thus 100% in our series; LUF was well tolerated by the patients, and no technical complications were observed. In our opinion, the diagnostic DSA and CT/LUF is justified only for the typification of suspected focal nodules unsuitable for biopsy: in other instances, especially in case of HCC with positive biopsy/clinical findings and focal nodular mass, the technique should be directly employed as a therapeutic approach, with the injection of lipiodolized agents to treat both primary and daughter nodules after surgery in operable patients, and to begin chemoembolization treatment in patients with intrahepatic polyfocal diffusion. DSA and LUF are therefore of primary importance in the diagnosis and therapeutic flow-chart of HCC associated with hepatic cirrhosis.