Background: CT-guided transthoracic core needle biopsy (TCNB) is a minimally invasive diagnostic procedure and a useful radiological method for diagnosing pleural lesions smaller than 10 mm in the presence of loculated pleural effusion. The purpose of this study was to retrospectively assess the diagnostic accuracy of CT-guided TCNB of small pleural lesions and determine the incidence of complications. Methods: This retrospective study included a total of 56 patients (45 men and 11 women; mean [± SD] age, 71.84 ± 10.11 years) with small costal pleural lesions (thickness of < 10 mm) who underwent TCNB performed at the Department of Radiology from January 2015 to July 2021. One of the inclusion criteria for this study was a loculated pleural effusion greater than 20 mm, with a nondiagnostic cytological analysis. Sensitivity, specificity and positive as well as negative predictive values (PPV, NPV) were calculated. Results: The sensitivity of CT-guided TCNB for the diagnosis of small pleural lesions in this study was 84.6% (33 of 39), specificity 100% (17 of 17), PPV 100% (33 of 33), and NPV 73.9% (17 of 23), while diagnostic accuracy was 89.3% (50 of 56). The overall diagnostic contribution of TCNB in our study is comparable with the results of other recent reports. Loculated pleural effusion was considered a protective factor since no complications were noted. Conclusion: CT-guided transthoracic core needle biopsy (TCNB) is an accurate diagnostic method for small suspected pleural lesions with a near-zero complication rate in the presence of loculated pleural effusion.