Systemic lupus erythematosus (SLE) is a chronic, multi-organ inflammatory disease of autoimmune origin. In some cases, SLE may be the first symptom of cancer. In rheumatology,  paraneoplastic syndromes manifest as symptoms of inflammation of joints, muscles, and blood vessels caused by cancer, but not directly related to tumor invasion or the presence of metastases. SLE as a paraneoplastic syndrome has been observed in patients with lymphoma, breast cancer, lung cancer, and rarely gastrointestinal cancer. Here, we present the case of a 69-year-old man with an inflammatory rash on his face, neck, upper limbs and back, as well as oral ulcers, arthritis, and weight loss. Laboratory tests revealed pancytopenia, low complements C3 and C4, and positive antinuclear and anti-ribosomal protein P antibodies. Thoracic, abdominal and pelvic CT scans showed pleural effusion, a single enlarged mediastinal lymph node, irregular thickening of the splenic flexure of the colon and splenomegaly. Colonoscopy revealed a polypoid lesion in the distal transverse colon and descending colon; histopathological examination showed adenocarcinoma NOS low grade. Treatment consisted of high - dose glucocorticoids and hydroxychloroquine. As a result of the treatment, the skin and mucosal lesions, as well as the arthritis, significantly decreased. In December 2025, a partial colon resection was performed. Since the operation, there have been no signs of SLE activity. Any systemic connective tissue disease, including SLE, can be a paraneoplastic syndrome. To date, only one case of paraneoplastic SLE has been reported in patients with colon cancer. Particular attention should be given to the possibility of cancer in SLE cases involving severe skin lesions, general symptoms and an older age at the onset. Anti-ribosomal P antibodies are mainly known as highly specific markers for SLE, but research has indicated they can also be elicited in cancers, potentially resulting from tumor-induced immunogenicity. Many studies indicate that ribosomal P protein or antibodies to P protein may become a new potential diagnostic, prognostic biomarker or promising therapeutic target in colon cancer.