The laboratory is frequently the primary source for making the diagnosis of Lyme borreliosis when the symptoms are vague and the clinical hallmarks are missing. However, the temptation to interpret the laboratory results out of context from the clinical history and presentation should be avoided since the laboratory tests for evidence of B. burgdorferi infection can also be problematic. These problems have included sensitivity/specificity problems, lack of standardization of both methology and interpretation, and lack of routine direct evidence (ie culture) testing. These problems are discussed as well as possible solutions. It should be noted that meaningful results can usually be obtained from these tests if caution is used in their interpretation and the clinical symptomatology, history, and examination are integrated with the laboratory results.