It can be diagnosed via blood study that identifies fat particles. The patient must fast overnight to prevent interference from fat in the blood due to food intake. The criteria for this (without the involvement of cholesterol-lowering drugs) are total cholesterol levels below 120 mg/dL and LDL cholesterol levels under 50 mg/dL.

Hypobetalipoproteinemia is a disorder consisting of low levels of LDL cholesterol or apolipoprotein B, below the 5th percentile. The patient can have hypobetalipoproteinemia and simultaneously have high levels of HDL cholesterol.

Notably, in people who do not have the genetic disorder hypobetalipoproteinemia, a low cholesterol level may be a marker for poor nutrition, wasting disease, cancer, hyperthyroidism, and liver disease.

Hypolipoproteinemia, hypolipidemia, or hypolipidaemia (British English) is a form of dyslipidemia that is defined by abnormally lowered levels of any or all lipids and/or lipoproteins in the blood. It occurs through genetic disease (namely, Hypoalphalipoproteinemia and Hypobetalipoproteinemia), malnutrition, malabsorption, wasting disease, cancer, hyperthyroidism, and liver disease.

Typically in hypobetalipoproteinemia, plasma cholesterol levels will be around 80–120 mg/dL, LDL cholesterol will be around 50–80 mg/dL.

Apolipoprotein B deficiency (also known as "Familial defective apolipoprotein B-100") is an autosomal dominant disorder resulting from a missense mutation which reduces the affinity of apoB-100 for the low-density lipoprotein receptor (LDL Receptor) . This causes impairments in LDL catabolism, resulting in increased levels of low-density lipoprotein in the blood. The clinical manifestations are similar to diseases produced by mutations of the LDL receptor, such as familial hypercholesterolemia. Treatment may include, niacin or statin or ezetimibe.

It is also known as "normotriglyceridemic hypobetalipoproteinemia".

According to the American Heart Association in 1994, only total cholesterol levels below 160 mg/dL or 4.1 mmol/l are to be classified as "hypocholesterolemia". However, this is not agreed on universally and some put the level lower.

Possible causes of low cholesterol are:

- statins

- hyperthyroidism, or an overactive thyroid gland

- adrenal insufficiency

- liver disease

- malabsorption (inadequate absorption of nutrients from the intestines), such as in celiac disease

- malnutrition

- abetalipoproteinemia - a rare genetic disease that causes cholesterol readings below 50 mg/dl. It is found mostly in Jewish populations.

- hypobetalipoproteinemia - a genetic disease that causes cholesterol readings below 50 mg/dl

- manganese deficiency

- Smith-Lemli-Opitz syndrome

- Marfan syndrome

- leukemias and other hematological diseases