In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver (EASL) recommendations, as a criterion for characterizing small (1-3 cm) nodules in cirrhosis. A total of 72 nodules (1-2 cm, n = 41; 2.1-3 cm, n = 31) detected by ultrasonography in 59 patients with cirrhosis were included in the study. When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography, the lesion was considered to be hepatocellular carcinoma (HCC) according to EASL criteria. When one or both techniques showed negative results, ultrasound-guided biopsy was performed. In cases with negative results for malignancy or high-grade dysplasia, biopsy was repeated when an increase in size was detected at the 3-month follow-up examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%; 44% of 1-2-cm nodules and 84% of 2-3-cm nodules). Fourteen nodules (19.4%) had negative results with both techniques (hypovascular nodules). Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion, the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of small nodules in cirrhosis; thus, biopsy frequently is required in this setting. Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as highly suspicious for HCC.