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Introduction Lupus erythematosus (LE) is an autoimmune disease often treated with antimalarial drugs. The prolonged use of chloroquine and hydroxychloroquine can cause hyperpigmentation in the skin, oral mucosa and retinal pigment epithelium, which in turn can trigger toxicity in this epithelium, which in some cases causes vision loss. The objective of the present work was to establish the association between the presence of oral pigmented macules by antimalarial and secondary retinal toxicity. Methods A total of 105 patients diagnosed with LE being treated with chloroquine/hydroxychloroquine were evaluated. All patients were ophthalmologically evaluated for retinopathy screening. When the patient showed oral hyperpigmented maculae, an incisional biopsy was performed with the corresponding histopathological study with informed consent. The variables were compared using the chi-square test for quantitative variables and the non-parametric Mann–Whitney U-test for categorical variables. The confidence level was established at 95%, and p-values of ≤0.005 were considered statistically significant. Results Only 9.5% of the patients showed oral brown spots. Histopathologically, 100% of the oral macules showed characteristics of oral pigmentation by drug and 100% ophthalmological parameters of normality. Two patients presented with a diagnosis of pre-retinopathy, but none showed oral lesions. Conclusion Hyperpigmented macules in the buccal mucosa in lupus patients receiving antimalarial treatment are not frequent and do not represent a predictive finding of toxicity of the drug.