Transabdominal ultrasound not always allows to determine the nature of ascites based solely on its characteristics. Aim: The aim of the study was to present difficulties in determining the nature of ascites using transabdominal ultrasonography solely based on extra-organ lesions as well as, after the inclusion of the overall abdominal assessment and the clinical picture. Materials and methods: A total of 18 patients with non-neoplastic ascites and 62 patients with neoplastic ascites whose final diagnosis was based on cytological and histopathological findings were evaluated between 2005 and 2015. Abdominal ultrasound was performed to detect the presence of fluid in all accessible spaces, and, additionally, to determine the presence of potential peritoneal tumor implants as well as to evaluate the parietal peritoneum and the greater omentum. Different digital ultrasound machines equipped with 3–6 MHz and linear 7–12 MHz transducers were used in the study. Double-sided Fisher’s exact test with statistical significance at p < 0.05 was used for the analysis of the obtained results. Results: Statistically significant differences between benign and neoplastic ascites were found for: anechoic peritoneal fluid (<0.0001); fluid and thickened omentum with smooth surface (<0.0001); fluid and thickened omentum with smooth surface and varices (0.01); fluid and thickened omentum with hypoechoic foci (0.049); fluid and thickened omentum with tumor implants (0.009). The inclusion of the overall assessment of abdominal organs and the clinical data allowed for an improvement in ultrasonographic diagnostic accuracy in benign and neoplastic ascites from 83.3% and 67.7% to 94.4% and 93.5%, respectively. Conclusions: When used alone, an assessment of acoustic fluid characteristics and extra-organ peritoneal lesions limits the possibility to differentiate between benign and malignant ascites. These results improve after the inclusion of sonographic assessment of all abdominal organs in combination with clinical data.