Purpose <p>This study aimed to determine whether the presence of intraductal carcinoma of the prostate or invasive cribriform carcinoma correlates with homologous recombination repair or mismatch repair gene alterations in patients with prostate cancer who have not undergone prior systemic treatment.</p> Materials and methods <p>We conducted a retrospective review of 347 systemic treatment-naïve prostate cancer patients who underwent genomic testing between January 2018 and May 2024 at a single tertiary center. Clinical and genomic characteristics were compared between groups with and without intraductal carcinoma of the prostate or invasive cribriform carcinoma. Predictive factors for homologous recombination repair gene mutations were identified through logistic regression.</p> Results <p>Among the study population, 73.2% demonstrated intraductal or cribriform histologic features. Mutations in homologous recombination repair genes were detected in 24.8% of those with these features, and in 22.6% of those without. Mutations in mismatch repair genes occurred in 2.8% and 1.1% of the respective groups. No differences were observed in prostate-specific antigen levels, microsatellite instability, or tumor mutational burden. Logistic regression analysis identified Grade Groups (<i>P</i> &lt; 0.001) and younger age at diagnosis (<i>P</i> = 0.041) as significant predictors of homologous recombination repair gene alterations. The presence of intraductal or cribriform patterns, however, did not predict such mutations (<i>P</i> = 0.827).</p> Conclusion <p>The presence of intraductal carcinoma or cribriform growth patterns was not associated with increased likelihood of mutations in homologous recombination repair genes. These findings support the use of clinical parameters such as age and Grade Group, rather than histologic subtype alone, in guiding decisions for genetic testing.</p>