Thalidomide has been reported as efficacious in refractory cutaneous lupus erythematosus (LE). The most fearful side-effects are teratogenicity and neuropathy. We reported clinical efficacy of long-term low-dose use of thalidomide in 65 patients with LE, emphasizing the prevalence of adverse effects, especially of neuropathy and its related factors. Data obtained from medical records included age, sex, disease duration, and the presence of diagnostic criteria for systemic lupus erythematosus (SLE), the extent and activity of cutaneous lesions and previous treatments. Sixty-three patients (98.9%) presented complete or partial improvement with thalidomide therapy. Drowsiness occurred in 50 patients (77%). Twenty-eight patients (43.2%) presented neuropathy symptoms. Nerve conduction studies were done in 21 (75%) of them and were abnormal in 12 (57%). With the interruption of thalidomide, 24 (82.5%) had complete or partial improvement of neuropathy symptoms and 23 (82%) of them had cutaneous relapse. There were no significant differences between those who developed or not neuropathy in treatment duration, age, total dose and systemic versus cutaneous LE. In conclusion, thalidomide can be used in refractory cutaneous LE with great efficacy and relative security. Controlled studies with schemes with lower doses or intermittent usage or alternative drugs are wanted to reduce the burden of cutaneous morbidity of lupus erythematosus.