Skin and soft tissue infections are often seen in clinical practice, yet their microbiological diagnosis is among the most complex of laboratory tasks. The diagnosis of a skin and a soft tissue infection is generally based on clinical criteria and not microbiological results. A microbiological diagnosis is reserved for cases in which the etiology of infection is required, e.g., when the infection is particularly severe, when less common microorganisms are suspected as the causative agent (e.g. in immunocompromised patients), when response to antimicrobial treatment is poor, or when a longstanding wound does not heal within a reasonable period of time. We report the indications, sampling and processing techniques, and interpretation criteria for various culture types, including quantitative cultures from biopsy or tissue specimens and semiquantitative and qualitative cultures performed on all types of samples. For non-invasive samples taken from open wounds, application of the Q index to Gram stains is a cost-effective way to standardize sample quality assessment and interpretation of the pathogenic involvement of the different microorganisms isolated from cultures. All these issues are covered in the SEIMC microbiological procedure number 22: Diagnóstico microbiológico de las infecciones de piel y tejidos blandos (Microbiological diagnosis of infections of the skin and soft tissues) (2nd ed., 2006, www.seimc.org/protocolos/microbiologia).