Background: Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L-1, may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood. Methods: Using a primary care resource, comprising more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed. Results: Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias and myelodysplastic syndromes. Odds ratios [95% confidence interval (CI)] for viral infections were 2.32 (1.84-2.91), 2.80 (2.20-3.57) and 4.77 (3.22-7.07) for subnormal (≥1.5-1.8 G L-1), mild (≥1.0-1.5 G L-1) and moderate-severe (≥0.0-1.0 G L-1) neutropenic individuals, respectively (all P < 0.001). Likewise, odds ratios (95% CI) for haematological malignancies were 3.23 (2.35-4.45), 8.69 (6.58-11.47) and 46.03 (33.98-62.35 ), for the same neutropenia levels, respectively (all P < 0.001). Thus, the lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively. Conclusions: Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented here support focusing attention to viral diseases and haematological malignancies when neutropenia is observed.