Introduction and Hypothesis <p>There is significant variation in interstitial cystitis/bladder pain syndrome (IC/BPS) biopsy processing and reporting. The objective of this study was to review pathology reports from a large IC/BPS patient cohort to identify differences in findings. We hypothesize that variation in IC/BPS bladder biopsy reporting might be most frequent when it comes to mast-cell counts.</p> Methods <p>We performed a retrospective analysis of 461 diagnostic pathology reports collected from our IRB-approved prospective study of patients diagnosed with IC/BPS at the Urology Clinic at Wake Forest Baptist Hospital from October 2011 to July 2023 (IRB00018552). Data were assigned as continuous or categorical variables. Groups were compared using Student’s <i>t</i> test, Mann–Whitney, or Chi-squared tests.</p> Results <p>Staining strategy for mast-cell visualization differed between pathologists and included in order of frequency mast-cell tryptase (TPSAB1), CD117 (KIT), unspecified stain, a combination of stains, and toluidine blue. Mast-cell count was reported as a single number, range, or qualitatively. Pathologists used units of high-powered field (HPF), mm², or did not specify. As expected, average mast-cell count per HPF was significantly lower than per mm² across all stains (<i>p</i> &lt; 0.0001). Average count with KIT was significantly lower than TPSAB1 (<i>p</i> &lt; 0.0001). This trend remained significant when considering only KIT and TPSAB1 counts per HPF (<i>p</i> = 0.0007). Additionally, reports identified squamous metaplasia, acute inflammation, and/or chronic inflammation.</p> Conclusions <p>There is a lack of standardization regarding histological analysis of bladder biopsies from patients with IC/BPS, leading to inconsistent data and confusion surrounding the significance of pathology report findings.</p>