Cutaneous lupus erythematosus (CLE) is a disfiguring disease that can exist as an independent entity or as a manifestation of systemic lupus erythematosus (SLE) where up to 70% of patients experience lesions during their disease course. Subacute CLE (sCLE) is an inflammatory lesion with associated erythema in papulosquamous or annular formations. Typically, sCLE does not scar but depigmentation can occur. Importantly, sCLE is associated with a higher progression to SLE. Discoid lesions (DLE) are often circular and frequently lead to alopecia and scar formation. sCLE lesions have a higher propensity for photoprovocation and a more robust inflammatory infiltrate following ultraviolet (UV) B exposure. The pathogenic mechanisms which govern the differences between DLE and sCLE remain poorly defined, and this is reflected by the refractory nature of cutaneous lesions to usual lupus therapies. In this study, we evaluated the transcriptional profiles of 26 DLE and 23 sCLE biopsies and compared them to control skin and to each other in order to develop a comprehensive understanding of the similarities and differences between these two clinical subtypes.