Several studies have identified a functional single nucleotide polymorphism 1858C/T in the PTPN22 gene to be associated with several autoimmune diseases. Association studies of this polymorphism with familial and sporadic systemic lupus erythematosus (SLE) have shown some discrepancies. To our knowledge, this is the first study that includes only pediatric-onset SLE patients. We performed a case-control association study in 250 unrelated Mexican patients with childhood-onset SLE consisting of 228 cases with sporadic SLE and 22 cases with familial SLE and 355 healthy controls. We observed a statistically significant difference in the frequency of the PTPN22 1858T allele between SLE patients (3.4%) and healthy controls (1.1%) (P=0.0062, odds ratio (OR) 3.09 (95% confidence interval 1.32-7.21)). The association was also observed when only sporadic cases were analyzed (OR=3.19). Our results support the association of the PTPN22 1858T allele with sporadic childhood-onset SLE in Mexican population.