There are no definitive criteria for the presence of malignancy in the opposite lobe in cases of unilateral lobectomy due to a thyroid mass in which the malignancy was diagnosed histologically. Study design is retrospective, cross sectional study. The present study included patients who underwent a lobectomy in our clinic between 2001 and 2016 with an initial diagnosis of atypia with undetermined significance or suspected malignancy according to fine-needle aspiration biopsy and adult patients who received a thyroidectomy based on thyroid cancer detected in pathological examinations. Tumor histopathological diagnosis, tumor size, and capsular, vascular, or lymphatic invasion were assessed in patients who received thyroid lobectomy. The presence of a multifocal tumor (52.3%) significantly increased the risk of malignancy in the opposite lobe over the risk association with a unifocal tumor (8.9%; p < 0001). In patients with a tumor diameter greater than 4 cm (83.3%), the risk of malignancy in the opposite lobe was higher than that in patients with a tumor diameter less than 4 cm (22.3%; p < 0.001). Significant differences were not observed between groups with and without vascular or capsular invasion of the opposite lobe (p = 0.913 and p = 0.840, respectively). We determined risk factors for the presence of multifocal disease in unilateral lobectomy materials; an aggressive tumor subtype and a size larger than 4 cm are the most important factors that increase the risk of malignancy in the opposite lobe.Level of evidence Level 4-Case-control studies.