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Purpose: To estimate the prevalence of USP8, USP48, and BRAFmutations in patients with Cushing’s disease (CD) from the Indian subcontinent, and determine their genotype-phenotype correlation. Methods: We prospectively recruited 46 patients with CD who underwent surgery between September 2015 and July 2019 at our institute. Fresh frozen tumour tissue was obtained in all patients. Using Sanger sequencing, the presence of somatic USP8mutations was documented and the frequency of USP48and BRAFmutations in USP8wild-type corticotroph adenomas was determined. Clinical, hormonal, and surgical data were then compared between USP8-, USP48- and BRAF-variant carriers and patients with wild-type tumours. Results: Signature USP8mutations were detected in 17 (37%) patients. Of the 29 USP8wild-type adenomas, 4 (13.8%) harboured USP48mutations, one of them being a splice-site mutation that has previously not been described. BRAFmutations were not found in any of the 29 patients. Corticotroph adenomas with USP8mutations had a higher incidence of Crooke’s hyaline change than wild-type tumours (70.6 vs. 37.9%, p= 0.032). Adenomas with USP48mutations had a higher rate of cavernous sinus invasion than their wild-type counterparts (50 vs. 4%, p= 0.042). No other significant phenotypic difference could be established between mutant and wild-type tumours. Conclusions: The prevalence of USP8mutations in our series of patients with CD was 37%. The prevalence of USP48mutations in USP8wild-type adenomas was 13.8%, including a novel splice-site mutation. BRAFmutations were not found in any USP8wild-type tumour. USP8-mutants showed significantly more Crooke’s hyaline change and USP48-mutants were more likely to demonstrate cavernous sinus invasion.