Background: Autoimmune vesiculobullous disorders (AVBDs) are a heterogeneous group of immune-mediated blistering diseases characterized by considerable clinical overlap, making accurate diagnosis challenging. Clinicohistopathological correlation plays a crucial role in establishing the diagnosis, particularly in settings where direct immunofluorescence is not routinely available.

Methods: This hospital-based cross-sectional observational study was conducted in the Department of Dermatology, Venereology and Leprosy, Amaltas Institute of Medical Sciences, Dewas, Madhya Pradesh. Ninety-two patients with clinically suspected, untreated autoimmune vesiculobullous disorders presenting with fresh lesions were enrolled. All patients underwent detailed clinical evaluation, Tzanck smear examination, and skin biopsy for histopathological assessment. Clinical diagnoses were compared with histopathological findings to determine clinicohistopathological concordance.

Results: The majority of patients were females (73.91%) and belonged to the 41–50-year age group (27.17%). Oral mucosal involvement (55.43%), vesicular lesions (76.09%), and positive Nikolsky's sign (79.34%) were the predominant clinical findings. Pemphigus vulgaris was the most common clinical (64.13%) and histopathological (60.87%) diagnosis, followed by pemphigus foliaceus and bullous pemphigoid. Suprabasal cleft formation (60.87%) and acantholysis (65.22%) were the principal histopathological findings. Tzanck smear was positive in 86.96% of cases, with acantholytic cells identified in the majority. Overall clinicohistopathological concordance was 93.48%, with excellent agreement between clinical and histopathological diagnoses (Cohen's κ = 0.823; p < 0.001).

Conclusion: Pemphigus vulgaris was the predominant autoimmune vesiculobullous disorder in this cohort. A combined approach incorporating clinical examination, Tzanck smear, and routine histopathological evaluation demonstrated excellent diagnostic accuracy and remains a practical, reliable, and cost-effective strategy for diagnosing autoimmune vesiculobullous disorders, particularly in resource-limited settings.