Clinical decision-making and biomedical research heavily rely on imaging techniques to visualize tissue morphology. To examine tissues in detail, it is necessary to use special histochemical stains to enhance contrast. This meta-analysis aimed to assess the sensitivity and specificity of these stains in diagnosing oral pathologic specimens. We conducted a search in 8 databases, including EMBASE, PubMed, Web of Science, Scopus, ProQuest, Ovid, Cinahl, and Cochrane, up to June 2022. Of 87,393 studies, 41 articles were selected for inclusion in our study. The results revealed that the specificity and sensitivity of the special histochemical stains were 86% with confidence interval (CI) 95%: 80%–90% and 83% with CI 95%: 75%–89%, respectively. Among the stains evaluated, toluidine blue, Papanicolaou, silver stain, Giemsa, Gram, feulgen, and periodic acid–Schiff (PAS) were the most frequently used for the detection of malignancy, premalignant lesions, dysplasia, and candidiasis. The specificity and sensitivity of each stain were analyzed individually, considering the type of specimen. Toluidine blue was the most commonly utilized special histochemical stain, particularly effective, for detecting malignancy, with a specificity of 97% with CI 95%: 88%–99% and sensitivity of 76% with CI 95%: 56%–89%. In conclusion, special histochemical stains are effective in diagnosing oral lesions, exhibiting reasonable specificity and sensitivity, especially in cases of premalignant and malignant lesions. Based on the reviewed articles in our study, the silver stain was identified as highly sensitive, while Giemsa and Papanicolaou stain exhibited the highest specificity.