Aim: The aim of this study was to evaluate the feasibility of adequacy, accuracy, and safety of ultrasound-guided tru-cut biopsy in managing malignant and benign abdominopelvic masses in a selected population and critically discuss some issues in different situations, which deserve some reflections on those practices. Materials and Methods: This is a retrospective study involving 42 patients who underwent transvaginal or transabdominal tru-cut biopsy between August 2017 and November 2021. The inclusion criteria were poor health status or primary inoperable advanced tumor, suspicion of recurrence or metastasis to the ovaries or peritoneum in gynecological and non-gynecological pelvic malignancies. Tissue samples were considered adequate if it was possible to determine the origin of the tumor, and immunohistochemistry could be performed. Diagnostic accuracy was assessed considering the agreement between tru-cut biopsy histology and final postoperative histology. Results: It total, 44 biopsies were obtained from 42 patients (2 patients had repeat biopsies). The pathologist considered all pathological samples adequate (adequacy 100%). The final histology was consistent with tru-cut biopsy diagnosis in all but 2 cases (diagnostic accuracy 88.2%). If we consider only the cases that have carried out at least two diagnostic samples, accuracy rose to 94.1%. Pathological examinations from tru-cut samples showed 2 benign lesions (4.8%) and 40 malignant tumors (95.2%), divided into 19 advanced primary inoperable ovarian cancers, 7 primary advanced cervical cancers, 4 recurrent endometrial cancers, 3 recurrent cervical cancers, 3 recurrent ovarian cancers, 1 case of primitive peritoneal malignancy (leiomyosarcoma), and 3 non-gynecological cancers with a strong suspicion of metastases at ultrasound (2 cases of ovarian, colorectal cancer metastasis, and 1 case of pelvic site type B lymphoma metastasis). However, one case of minor complication related to the procedure was reported but not significant. Conclusions: The diagnostic adequacy, accuracy of the tru-cut biopsy, and safety were high. Pathological samples are representative of the disease and suitable for histological and immunohistochemical analysis.