Importance Although the most recent American Joint Committee on cancer staging guidelines for ocular surface squamous neoplasia place a heightened emphasis on biopsy and histopathologic analysis, the interpretation and clinical relevance of these staging criteria are not always clear. We address limitations of using histopathologic analysis to predict clinical outcomes and suggest less‐invasive assessments. Background To investigate the impact of histopathologic depth of invasion on outcomes for tumours with the common presentation of multiple structure involvement. Design Retrospective chart review at tertiary institution. Samples Of 41 eyes with ocular surface squamous neoplasia between 2012 and 2017, 27 tumours involving multiple ocular structures clinically were included. Methods Biopsied tumours were determined to be invasive beyond the basement membrane or non‐invasive; non‐biopsied tumours were clinically identified with unknown depth of invasion. Outcomes were compared using Fisher's exact or Student's t tests. Main Outcome Measures Proportion of tumours cured, recurred and/or persisting. Results Twelve tumours (44%) received primary excisional biopsy, 10 (37%) received chemotherapy without biopsy and 5 (19%) received chemotherapy and biopsy. Clinical diagnosis was correct in all biopsied cases. While there were no significant differences in outcomes between invasive vs non‐invasive tumours or treatments, there was a trend toward larger basal diameter in recurrent tumours regardless of treatment. Conclusions and Relevance When ocular surface squamous neoplasia tumours with similar clinical involvement were compared, histopathologic depth of invasion was not predictive of clinical outcomes. Future staging criteria may consider the potential of largest basal dimension for more accurate prognostication.