Peritoneal lesions cannot be definitively distinguished based on clinical and imaging characteristics alone. This study aimed to evaluate the reliability, diagnostic value, and diagnostic yield of ultrasound-guided percutaneous core needle biopsy (PCNB) for peritoneal lesions. A retrospective analysis of 129 patients who underwent PCNB for peritoneal lesions was performed to assessed technical completion and diagnostic yield. The results showed that ultrasound-guided PCNB is a safe and reliable diagnostic tool with high diagnostic yield for peritoneal lesions. Technical feasibility and diagnostic yield rates were 100% and 89.9%, respectively. The diagnostic yield was lower for patients with a known history of cancer and a short anteroposterior diameter of the target lesion. These findings suggest that ultrasound-guided PCNB could be considered as a first-line diagnostic tool for peritoneal lesions, as it offers a minimally invasive and accurate means of obtaining tissue samples for diagnosis.