Because most patients with lupus nephritis have a positive antinuclear antibody (ANA), ANA-negative lupus nephritis is a rare complication of systemic lupus erythematosus (SLE). In the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria for SLE, a negative ANA precludes further work-up of SLE. The following case discusses a patient with multiple negative ANA titers but was diagnosed with SLE based on the findings of the kidney biopsy showing lupus nephritis. Though ANA was negative, anti-double-stranded DNA (anti-dsDNA) and anti-Sjogren's syndrome-A (anti-SS-A) antibodies were high. This case highlights the nuances of SLE and further illustrates the challenges in making a diagnosis of SLE when serology alone is relied on for screening.