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Styrene is an important industrial chemical that the general population is exposed to at low levels. Previous research has suggested increased occurrence of leukemia and lymphoma among reinforced plastics workers exposed at high levels of styrene.We followed 73,036 workers of 456 small- and medium-sized Danish reinforced plastics companies from 1968 to 2011 and investigated the exposure-response relation between cumulative styrene exposure and incidence of lymphohematopoietic malignancies. We modeled styrene exposure from employment history, survey data, and historical styrene exposure measurements. We retrieved information on lymphohematopoietic malignancies from national cancer and patient registers.We identified 665 cases overall of 21 different lymphohematopoietic malignancies or combinations thereof, each with at least 20 cases, during 1,581,976 person-years of follow-up. Initial analyses suggested higher age, sex, and calendar year-adjusted incidence rate ratios (RRs) for acute myeloid leukemia, Hodgkin lymphoma, and T-cell lymphoma with higher estimates of cumulative styrene exposure. Accounting for time since exposure showed a trend by cumulative styrene exposure (P = 0.01) and a doubled risk (RR = 2.4; 95% CI, 1.2, 4.6) of acute myeloid leukemia following estimated high compared with estimated low cumulative exposure during the prior 15–29 years. We observed no increased risk following exposure during more recent years and less consistent risk patterns for Hodgkin lymphoma and T-cell lymphoma.This study, to our knowledge the largest epidemiologic study to date of occupational styrene exposure, suggests increased risk of acute myeloid leukemia following high styrene exposure with a latency period of about 15 years.