OBJECTIVE: The relationships between histopathology and imaging remain elusive and investigating the underlying causes of tumor microstructure that result in an imaging phenotype is of clinical importance. In the present study, cross-sectional guided biopsy specimens were used to correlate prebioptic magnetic resonance imaging (MRI) with immunohistochemical staining of histopathologic specimens using precise spatial biopsy localization. METHODS: Overall, 52 patients with atypical hepatocellular carcinoma (HCC) were included in the present analysis. All patients were imaged with a 1.5 T clinical scanner at least one month prior to biopsy. The contrast-enhanced dynamic sequences were analyzed with quantified signal intensities. The bioptic specimens were obtained by cross-sectional guided biopsy and was further analyzed for cell density, proliferation index (Ki 67), tumor-infiltrating lymphocytes, tumor-stroma ratio. RESULTS: Per high power field, the mean values of the histologic parameters were as follows: the tumor-stroma ratio was 17.1 ± 20, the cell count was 147.0 ± 60.3, the CD45 count was 7.3 ± 8.0 and the Ki 67-index was 16.9 ± 16.5%. There were no statistically significant correlations between the MRI signal intensities and cell count, tumor-stroma ratio and CD45 count. There was a moderate inverse correlation that was identified between arterial phase signal intensities and Ki 67 max (r=-0.41, P=0.002) and Ki 67 mean (r=-0.37, P=0.005). The signal intensities of the hepatobiliary phase were statistically significantly different between high and low proliferating HCC using thresholds of 20% and 10% (P=0.01 and P=0.02, respectively). The resulting AUC for the 10% threshold was 0.73 and 0.67 for the 20% threshold. CONCLUSION: DCE-MRI is associated with Ki 67 index in atypical HCC. The hepatobiliary phase could discriminate HCCs according to their Ki 67 index. Quantitative MRI could be used as an imaging-based surrogate for proliferative HCC. Further studies are needed to validate the present results.