In the present-day blood bank laboratory, we are surrounded by options with testing methods. Commonly used testing methods may include tube testing, gel testing, and red cell solid phase testing. Testing may be performed by manual methods or by automated methods and a blood bank laboratory may use multiple methods when problem-solving. This case studies presentation is intended to be diverse in order to cover the multiple methods that are in widespread use. By presenting separate cases that highlight the use of varied methods, the learner should be able to evaluate and understand the potential strengths and pitfalls of each method in regards to specificity and sensitivity in addition to improving overall serologic problem-solving skills.