Detection of absolute and relative lymphocytosis in otherwise asymptomatic elderly patients is very common in the primary care setting and frequently results in referral for screening of lymphoproliferative disorders. Since many B-cell chronic lymphoproliferative disorders (B-CLPD) are indeed asymptomatic at diagnosis in most patients with lymphocytosis, no sign of such a disorder is usually detected. Currently, specific guidelines for screening of patients with lymphocytosis are lacking. We investigated the practicability and clinical value of a single colour CD19 count performed by a primary care laboratory in order to improve the diagnostic follow-up of patients with lymphocytosis in a primary care laboratory. The capability of detecting monoclonal B-cell lymphocytosis and B-CLPD by CD19, was first confirmed in patient samples with known B-CLPD. Next, in a previously defined geographic area, a CD19 count was performed on all samples for patients aged ≥40 years with relative or absolute lymphocytosis but without neutropenia. Clinical follow-up, with a median of 4 years, was performed using both a survey among the requesting general practitioners and by analysis of the records of the referral hospitals within the borders of the defined area. A total of 520 cases with asymptomatic lymphocytosis were identified. In all cases, the CD19 count was performed; 207 (40%) showed increased values and 313 (60%) showed normal values. An increase in CD19 proved highly sensitive for detection of B-CLPD (98%, 95% CI; 94%-100%) with a high positive predictive value (57%, 95% CI; 50%-63%). The area under curve, the receiver-operating characteristic curve of the CD19 count (0.93, 95% CI; 0.91-0.96), was significantly higher compared to the absolute lymphocyte count (0.86, 95% CI; 0.83-0.89), especially in patients with moderate lymphocytosis. This study indicates that the CD19 count, performed by a primary care laboratory, is feasible and a promising tool for initial screening of lymphocytosis to discriminate B-CLPD from benign causes of lymphocytosis.