Human exposure to benzene is a global health problem. Benzene targets liver, kidney, lung, heart and the brain and can cause DNA strand breaks, chromosomal damage, etc. Benzene causes cancer in both animals and humans. Benzene has been shown to cause cancer in both sexes of multiple species of laboratory animals exposed via various routes.

Benzene increases the risk of cancer and other illnesses. Benzene is a notorious cause of bone marrow failure. Substantial quantities of epidemiologic, clinical, and laboratory data link benzene to aplastic anemia, acute leukemia, and bone marrow abnormalities. The specific hematologic malignancies that benzene is associated with include: acute myeloid leukemia (AML), aplastic anemia, myleodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML).

The American Petroleum Institute (API) stated in 1948 that "it is generally considered that the only absolutely safe concentration for benzene is zero."[46] The US Department of Health and Human Services (DHHS) classifies benzene as a human carcinogen. Long-term exposure to excessive levels of benzene in the air causes leukemia, a potentially fatal cancer of the blood-forming organs, in susceptible individuals. In particular, Acute myeloid leukemia or acute nonlymphocytic leukemia (AML & ANLL) is not disputed to be caused by benzene. IARC rated benzene as "known to be carcinogenic to humans" (Group 1).

Some women who inhaled high levels of benzene for many months had irregular menstrual periods and a decrease in the size of their ovaries. Benzene exposure has been linked directly to the neural birth defects spina bifida and anencephaly. Men exposed to high levels of benzene are more likely to have an abnormal amount of chromosomes in their sperm, which impacts fertility and fetal development.

The United States Environmental Protection Agency has set a maximum contaminant level (MCL) for benzene in drinking water at 0.005 mg/L (5 ppb), as promulgated via the U.S. National Primary Drinking Water Regulations. This regulation is based on preventing benzene leukemogenesis. The maximum contaminant level goal (MCLG), a nonenforceable health goal that would allow an adequate margin of safety for the prevention of adverse effects, is zero benzene concentration in drinking water. The EPA requires that spills or accidental releases into the environment of 10 pounds (4.5 kg) or more of benzene be reported.