<p>Histiocytic sarcoma (HS) is aggressive neoplasia arising from cells of the dendritic cell or macrophage lineage. Previously recognised negative prognostic factors are the presence of metastasis, anaemia, hypoalbuminemia, and thrombocytopenia. C-reactive protein (CRP) is an acute phase protein (APP), previously investigated as a prognostic marker in different neoplasms in human and veterinary medicine, including in Bernese Mountain dogs with histiocytic sarcoma, however no studies have evaluated serum CRP concentrations in all breeds with histiocytic sarcoma. Our study aimed to evaluate the prognostic value of serum CRP concentrations at the time of presentation and in different stages of the disease in a cohort of dogs, of different breeds, with histiocytic sarcoma. Dogs diagnosed with histiocytic sarcoma that not received any treatment prior to CRP measurement were included in the study. Patients were grouped according to the location of the primary tumour, tumour stage and treatment received (no treatment, localised treatment and systemic treatment)A Mann Whitney U was used to compare the CRP value with the stage and site of the tumour, while a Spearman’s correlation coefficient was used to compared the serum CRP with continuous variables. Thirty-five dogs were included. The median survival time for the entire population was 106&#xa0;days. Increasing serum CRP concentrations (p = 0.009) and younger age (p = 0.003) were associated with decreased survival time in the multivariable model. No correlation was found between serum CRP concentrations and the stage of the disease (p = 0.327) or the site of the primary tumour (visceral vs. periarticular p = 0.504). Serum CRP concentrations and age may be additional prognostic factors in patients with histiocytic sarcoma, that are worthy of further investigation in larger studies.</p>