A 21-year-old Quarter Horse mare presented with a chronic, progressively worsening left pelvic limb lameness of 3 weeks duration. The initial examination identified a consistent lameness at a walk. Neurological examination showed sensory and gait abnormalities consistent with left femoral nerve dysfunction. The horse minimally advanced the leg cranially and had a shortened stride length at the walk. During the stance phase, the heels of the left hind foot did not contact the ground and the horse quickly took weight off of the limb. Diagnostic imaging (ultrasound and nuclear scintigraphy) examinations did not reveal a cause. Severe lymphocytosis was identified on complete blood cell count (69,600 cells /uL; reference range: 1,500-4,000 cells/uL), suggestive of lymphoma. Postmortem examination revealed focal swelling of the left femoral nerve. Multiple masses were found in the stomach, large colon, adrenal gland, mesentery, heart, and meninges. The entire left pelvic limb was dissected and did not reveal other causes of the gait deficit. Histologic evaluation of the left femoral nerve revealed disseminated intermediate cell size B cell lymphoma, with an immunophenotype suggestive of plasmacytoid differentiation. These lymphocytes infiltrated the femoral nerve at the location of the focal nerve swelling, in addition to other peripheral nerves. This case highlights a horse with an atypical diagnosis of femoral nerve paresis caused by direct neoplastic lymphocyte infiltration, deriving from disseminated B cell lymphoma with plasmacytoid differentiation (neurolymphomatosis). Though rare, disseminated lymphoma with direct nerve infiltration should be considered in horses with peripheral neuropathies.