Cutaneous leishmaniasis (CL) is a chronic infectious disease characterized by extensive tissue destruction and profound extracellular matrix (ECM) remodeling. This study provides the first evidence of O-glycosylated oncofetal fibronectin (onf-FN) expression in human CL lesions. Immunohistochemical analysis revealed increased onf-FN expression throughout the inflammatory lesions, displaying a distribution pattern closely resembling that observed in human tumors and overlapping with total fibronectin expression. The detection of onf-FN in an infectious disease caused by protozoan parasites broadens the current understanding of ECM remodeling beyond cancer and developmental processes, suggesting that onf-FN may also participate in the host tissue response to chronic infection. Given the well-established biological functions of onf-FN in regulating cell adhesion, tissue remodeling, and repair, its expression in CL lesions raises important questions regarding its potential role in disease pathogenesis and parasite persistence. These findings identify onf-FN as a previously unrecognized component of the CL microenvironment, providing a foundation for future studies investigating its biological and clinical significance in parasitic diseases.