Thymosin beta 4 (T beta 4) is a peptide that has been shown in dermal, corneal, and cardiac preclinical injury models to potentially affect tissue protection, regeneration, and repair. Sacrococcygeal pilonidal sinus disease (SPSD) is a chronic inflammatory disorder associated with a high incidence of recurrence, chronic fistulation, and a challenging postoperative surgical wound healing process. Retrospectively, an immunohistochemical analysis was conducted to evaluate endogenous T beta 4 expression in excisional skin biopsies from patients with SPSD. Patient demographics (age, gender) and surgical procedure data were obtained from their electronic medical records. Two (2) samples were cut from each specimen and prepared for histopathological assessment: 1 from the inflamed sinus tracts containing hair and granulation tissue (chronic wound group) and 1 from the normal tissue at least 1 cm away from the sinus tract (control group). T beta 4 expression was evaluated in the epidermal, dermal/subcutaneous collagen, and vascular structures of the samples from the sinus tract and healthy tissue. Inflamed sinus tract tissue and noninflamed normal tissue adjacent to the sinus tract were sampled from each specimen to confirm the diagnosis of SPSD and to determine distribution and intensity of T beta 4 expression. Presence of cytoplasmic staining for T beta 4 was considered in favor of positive T beta 4 expression; intensity of T beta 4 expression was scored as 0 = no staining, 1 = mild, 2 = moderate, and 3 = strong level of expression. A total of 31 excisional skin biopsy specimens were available from 31 patients with SPSD (mean age 26.0 +/- 7.6 years, 25 [80.6%] men, 6 [19.4%] women) who underwent primary surgical closure. Demographic variables were analyzed using descriptive statistics. Data compliance with normal distribution was evaluated using the Kolmogorov-Smirnov and Shapiro-Wilk tests, and the Mann-Whitney U test was used for comparison of numerical data. P<.05 was considered statistically significant. Inflamed sinus tract tissue had significantly higher T beta 4 expression scores than noninflamed tissue samples in the epidermis (2.4 +/- 0.8 [1.0-3.0] versus 0.8 +/- 0.5 [0.0-2.0], P=.000), dermal/subcutaneous collagen (2.6 +/- 0.5 [2.0-3.0] versus 1.6 +/- 0.5 [1.0-2.0], P=.000), and vascular structure (2.6 +/- 0.5 [2.0-3.0] versus 1.1 +/- 0.3 [1.0-2.0], P=.000). Study findings indicate T beta 4 is endogenously expressed in normal skin tissue and is overexpressed in inflamed sinus tract tissue in patients with SPSD. Preclinical studies with a larger sample size are needed to enhance understanding of the potential role of T beta 4 in the inflammatory and tissue remodeling processes of SPSD by elucidating its mechanism of action at the molecular level, physiological role, and the therapeutic potential in dermal healing.