A vital step toward making the right diagnosis when dealing with infectious diseases is ordering the appropriate test. That implies having a certain idea of the range of possible organisms involved and directing your workup toward ruling in or out a specific agent. Of course, there will be cases where a more blind approach is in order and a large range of diagnostic possibilities should be considered. In those situations, smears and cultures for bacterial, mycobacterial, and fungal microorganisms are indicated. Also viral diseases should be considered in specific situations, such as febrile patients with disseminated maculopapular or vesicular rashes. However, just for practical purposes, it is better to take a syndromic approach, considering a range of possibilities regarding the etiology of the lesions and then, selecting the appropriate test. Let us take an example such as a patient with a sporotrichoid pattern of lesions. If the diagnosis to confirm is sporotrichosis, a fungal culture will be very sensitive and very specific. Pyogenic bacteria such as Staphylococcal aureus can also produce such a pattern. In these cases, a Gram stain and routine culture will be helpful. But, if the patient likes fishing, swimming, or diving besides gardening an atypical mycobacterial infection (M. marinum) also has to be listed in the differential. In such cases, a biopsy, acid-fast stain, and mycobacterial culture should also be considered, although recognizing this is a difficult diagnosis to make because of the low sensitivity of each individual test.