A cluster is a group of cases in a specific time and place that may or may not be greater than the expected rate. The aim of investigation in these types of situations often is to decide what the baseline rate for that time and place is.

Studies of disease clusters often are challenging because of the constraints of information available to investigators. Some of the biggest issues include:
- Rare health events
- Vague definition and/or heterogeneity of cases
- Lack of a population base for rate calculation
- Weak association and multiple risk factors
- Long induction periods
- Multiple comparisons
- Low-level, long-term, heterogeneous exposures
- Intense publicity
- Resource intensiveness of full investigations