Introduction. Liver metastasis represents a critical prognostic determinant in colorectal cancer (CRC). Precise imaging characterization of focal liver lesions directly impacts staging accuracy, treatment planning, and the need for additional diagnostic procedures. While various radiological modalities yield distinct imaging patterns that enable confident lesion characterization without further studies, the effect of chemotherapy on these patterns and their diagnostic specificity remains understudied. Aim. To compare the diagnostic yield of specific imaging features for focal liver lesions using grayscale ultrasound (US), contrast-enhanced ultrasound (CEUS), and contrast-enhanced computed tomography (CECT) in patients with CRC. Materials and Methods. This prospective study included 35 CRC patients (12 chemotherapy-naïve, 23 post-chemotherapy). All participants underwent comprehensive imaging evaluation comprising B-mode US, CEUS, and multiphase CECT. Imaging analysis focused on lesion characterization and identification of specific enhancement patterns enabling definitive lesion classification. Results. CEUS demonstrated superior performance in detecting specific diagnostic features compared to both grayscale US and CECT. Notably, CEUS maintained high pattern specificity in the post-chemotherapy cohort, while CECT specificity declined to 86%. Conclusion. CEUS provides optimal diagnostic yield for characterizing focal liver lesions while maintaining consistent performance post-chemotherapy. Standardized contrast enhancement patterns enable reliable metastasis-benign differentiation. Chemotherapy does not reduce the diagnostic effectiveness of CEUS, whereas with CT the specificity of patterns decreases. CEUS can serve as a first-line modality for lesion verification after initial US detection and as a valuable alternative to CT in cases of diagnostic uncertainty or contraindications to CT. © Ksenia V. Kozubova, Katerina A. Busko, Denis V. Nesterov, Ilya A. Burovik, Sergey S. Bagnenko, Roman A. Kadyrleev, Elvira S. Filonova, Valerya V. Nesterova, Pavel V. Balakhnin