Introduction: Leukemoid reactions in cancer are rare and associated with a poor prognosis. The mechanism driving paraneoplastic leukemoid reactions appears to be gain-of-function granulocyte-colony stimulating factor (G-CSF) secretion by tumour cells. Case Presentation: A 57-year-old male smoker presented with a one-year history of painless frank hematuria and three kilograms weight loss. Cystoscopy revealed a high-grade urothelial carcinoma with sarcomatoid differentiation. The patient was treated by radical cystoprostatectomy, bilateral pelvic lymph node dissection and formation of an ileal conduit. In the absence of bone marrow infiltrations, recurrence of the urothelial carcinoma three months later was associated with a paraneoplastic leukemoid reaction with a white blood cell count peaking at 82.62 × 10⁹/l. Unfortunately, his condition continued to deteriorate and he died shortly thereafter. Conclusion: Monitoring of white blood cell counts in paraneoplastic leukemoid reactions can be a useful indicator of response of the malignancy to chemotherapy or radiotherapy and an indication of relapse after treatment. Paraneoplastic leukemoid reactions are caused by G-CSF secretion by tumour cells and are associated with a poor prognosis. Whether G-CSF signaling plays a role in the aggressive nature of these cancers is currently unknown.