To explore the detection rates of clinically significant prostate cancer (csPCa; ISUP ≥2) in patients with a single MRI lesion that is visible or invisible on transrectal ultrasound (TRUS) during biopsy. Retrospective analyses of patients who underwent targeted and systematic biopsy of the prostate for one MRI-visible lesion (PI-RADS score ≥ 3) between 2017 and 2022. TRUS-visibility, PI-RADS score, and clinical parameters were recorded prospectively. Univariable and multivariable logistic regression models were used to identify predictors of csPCa. 277 consecutive patients with one MRI-visible lesion were identified. A correlating lesion on TRUS was present in 147/277 (53%). The median age, PSA level, and prostate volume were 68.0 years (IQR: 62.0-73.0), 7.3 ng/ml (IQR: 5.4-10.8) and 45.0 cc (IQR: 32.0-68.0), respectively. Baseline parameters were not significantly different between the two groups. CsPCa was detected in 59/130 (45%) without and in 102/147 (69%) patients with a corresponding TRUS lesion. In multivariable logistic regression analysis predicting csPCa, TRUS-visibility (OR: 2.13, CI: 1.14-4.03, p = 0.02) and PI-RADS score (PI-RADS 4: OR: 7.28, CI: 3.33-17.19; PI-RADS 5: OR: 13.39, CI: 5.27-36.83, p < 0.001) achieved independent predictor status. Bimodal-visible lesions more often harbored csPCa and were easier to target. TRUS-visibility of MRI lesions is an independent predictor of csPCa. Therefore, education in both modalities is essential. Despite MRI, the ultrasound should still be diligently examined.