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Background: Some authors consider adrenal lesions size of less than 4 cm as a positive cut-off limit to set the indications for minimally invasive surgery due to a lower risk of malignancy. Aim of this study is to report the risk of cancer for adrenal lesions measuring 4 cm or more in diameter, assessed as benign at preoperative workup (primary outcome), and to evaluate the feasibility and safety of laparoscopic adrenalectomy (LA) in these cases (secondary outcome). Methods: From January 1994 to February 2019, 579 patients underwent adrenalectomy. Fifty patients with a preoperative diagnosis of primary adrenal cancer or metastases were excluded. The remaining 529 patients were included and divided in five subgroups based on adrenal lesion size at definitive histology: group A, 4–5.9 cm (137 patients); group B, 6–7.9 cm (64 patients); group C, 8–9.9 cm (13 patients); group D, ≥ 10 cm (11 patients); group E, < 4 cm (304 patients). Each group was further divided based on diagnosis of benign or malignant lesions at definitive histology. Results: Four (2.9%) malignant lesions were observed in group A, 5 (7.8%) in group B, 2 (15.4%) in Groups C and D (18.2%) and 13 (4.3%) in Group E. Comparing the cancer risk among the groups, no statistically significant differences were observed. Operative time increased with increasing lesion size. However, no statistically significant differences were observed between benign and malignant lesions in each group comparing operative time, conversion and complication rates, postoperative hospital stay and mortality rate. Conclusions: Adrenal lesions measuring 4 cm or more in diameter are not a contraindication for LA neither in terms of cancer risk nor of conversion and morbidity rates, even if the operative time increases with increasing adrenal lesion diameter. Further prospective studies with a larger number of patients are required to draw definitive conclusions. [ABSTRACT FROM AUTHOR]