Cytologic criteria to distinguish hepatocellular carcinoma from nonneoplastic liver. The authors reviewed a series of fine-needle aspiration biopsy (FNAB) specimens of the liver to identify useful cytologic criteria to distinguish hepatocellular carcinoma (HCC) from nonneoplastic liver. Ten cytologic features were examined in this study: high cellularity, acinar pattern, trabecular pattern, hyperchromasia, pleomorphism, irregularly granular chromatin, uniformly prominent nucleoli, multiple nucleoli, increased nuclear/cytoplasmic ratio, and atypical naked hepatocytic nuclei. These features were examined in a series of 82 FNAB specimens from 52 patients with HCC and 30 patients with nonneoplastic lesions. With the use of a step-wise logistic regression analysis, three features were identified as predictive of HCC: increased nuclear/cytoplasmic ratio (P = 0.001), trabecular pattern (P = 0.002), and atypical naked hepatocytic nuclei (P = 0.03). When these three criteria were used, the sensitivity of diagnosing HCC by FNAB was 100%, and the specificity was 87%. 