A major limitation of performing hemiablative focal therapy (FT) for prostate cancer (PCa) is the possibility of accompanying significant cancer in the contralateral side of the prostate that is missed on prostate biopsy. We attempted to verify whether clinical and biopsy-related parameters can be used to predict the absence of significant cancer in the prostate lobe. Methods: We assumed that hemiablative FT could be performed in patients with low-risk PCa, with unilateral tumors as assessed by transrectal ultrasound-guided biopsy. We evaluated 214 patients who had undergone radical prostatectomy (RP) and fulfilled the eligibility criteria. Seemingly preserved lobes, defined by the absence of cancer on biopsy, were classified as lobes with no cancer (LNC), lobes with insignificant cancer (LIC), and lobes with significant cancer (LSC) according to RP pathology. Cases with an estimated tumor volume of <0.5 mL, a Gleason score of <7, and organ confinement without Gleason pattern 4 were classified as LIC. Univariate and multivariate logistic regression analyses were performed to identify predictors for LSC. Predictive accuracies of the multivariate models were assessed using receiver operating characteristic curve-derived areas under the curve. Results: Of 214 evaluated lobes, 45 (21.0%), 62, (29.0%), and 107 (50.0%) were classified as LNC, LIC, and LSC, respectively. Among the clinical and biopsy-related parameters, prostate-specific antigen density and prostate volume were identified as significant predictors for LSC in univariate regression analysis. However, multivariate analysis did not identify an independent predictor. Predictive accuracies of the multivariate models did not exceed 70.4%. Conclusions: Conventional parameters have limited value in predicting LSC in patients who are candidates for hemiablative FT.