Bosniak 2F renal cystic lesions feature morphologic characteristics between Bosniak I and III categories, the majority of which remain benign. However, a minor part of Bosniak 2F lesions may progress to malignancy. The purpose of this study was to assess Bosniak 2F cystic lesions during follow-up examinations by CEUS. One-hundred-and-twelve out of 364 patients with Bosniak 2F lesions underwent follow-up CEUS examinations between February 2008 and February 2020. Twelve out of 364 patients underwent renal surgery without follow-up CEUS. The progression rate of Bosniak 2F renal lesions detected by CEUS accounted for 7.1% (8/112 patients) after a mean of 12.9 months. The first follow-up CEUS revealed 75% of progressions (6/8), the remaining 25% (2/8) of progressions were detected during second follow-up CEUS. Underlying clear-cell renal cell carcinoma was histopathologically validated in 5/8 progressive complex cystic renal lesions. Stable sonomorphologic features were observed in 92.1% (104/112 patients). CEUS depicts a promising diagnostic imaging modality in the diagnostic work-up and follow-up of complex renal cystic lesions at higher spatial and temporal resolutions than CT or MRI. Its excellent safety profile, its easy and repeatable accessibility, and low financial costs render CEUS an attractive and powerful alternative imaging tool for monitoring complex renal cystic lesions.