Objectives: Our objective was to evaluate the diagnostic accuracy of clinical diagnoses in patients with chronic conjunctival lesions (CCLs) in relation to prevalence data and to identify clinical features that improve diagnostic performance. Methods: Retrospective data were collected for all patients with CCLs at a tertiary eye clinic between 2006 and 2024. A total of 1304 patients were reviewed; 391 had available histopathological data. Results: Misclassification was the highest for clinically benign, non-melanocytic, non-degenerative CCLs (referral rates: 0.446; positive predictive value PPV: 0.289). The referral rates for histology assessment were comparable for malignant melanocytic and non-melanocytic CCLs (0.923 and 0.989, respectively) and for benign melanocytic and non-melanocytic CCLs (0.319 and 0.446, respectively). In contrast, the diagnostic agreement was double for melanocytic malignant CCLs (0.800 vs. 0.391) and triple for melanocytic benign CCLs (0.934 vs. 0.289) compared with non-melanocytic CCLs. However, the limbal involvement increased the odds ratio (OR) for proper diagnostic performance to 7.0 (95% confidence interval (CI): 2.7–19.1), whereas the limbal overlapping increased the OR to 11.2 (95% CI: 4.0–35.9) among malignant CCLs. Conclusions: The clinical diagnosis of non-melanocytic CCLs is less frequently and less accurately confirmed histologically. In this CCL subgroup, where the lesion involves or overlaps the limbus, the likelihood of malignancy is increased sevenfold to elevenfold.
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