A risk factor is anything that increases a person's chance of getting a disease such as cancer. Risk factors for cancer are either lifestyle-related, environmental, or genetic (inherited).

Examples of lifestyle-related risk factors for some types of cancer include smoking, a low-fiber diet, or unprotected exposure to strong sunlight. The only proven lifestyle-related risk factor for leukemia is smoking. Although many people know that smoking is responsible for most cancers of the lungs, mouth, throat, and larynx, few realize that it can affect cells that do not come into direct contact with smoke. Cancer-causing substances in tobacco smoke are absorbed by the lungs and can spread through the bloodstream to many parts of the body.

Environmental risk factors are influences in our surroundings such as radiation, chemicals, and infections. High dose radiation exposure (such as being a survivor of an atomic bomb blast or nuclear reactor accident) increases the risk of developing CML, but not CLL. Exposure to Agent Orange, a defoliant containing dioxin that was used during the Vietnam War, has been linked to an increased risk of CLL (but not CML). No strong links to other chemicals or toxins in the environment have yet been identified.

There is conflicting evidence about whether electromagnetic field (EMF) is a potential risk factor for developing leukemia. Several large studies are in progress at this time to further investigate this question. EMFs are a type of energy that occurs near very high-voltage power lines. Most studies published so far suggest either no increased risk or a very slightly increased risk of developing chronic leukemia. Some studies suggest that EMF exposure may be a risk factor for acute leukemia in children.

The only inherited risk factor known for chronic leukemia is that first-degree relatives (parents, siblings, or children) of CLL patients have a two-to-fourfold increased risk for this cancer.