Screening for latent tuberculosis infection (LTBI) is recommended before treatment with biologics is initiated in patients with psoriasis or inflammatory bowel disease (IBD). Our objective was to evaluate the effect of underlying disease (psoriasis or IBD) on the risk of LTBI diagnosis prior to anti-tumor necrosis factor-alpha (TNF-α) therapy. During a two-year period LTBI diagnosis rate was compared in consecutive patients with psoriasis or IBD (Crohn's disease or ulcerative colitis). IBD patients (n = 33) had significantly smaller tuberculin skin testing compared to psoriasis patients (n = 30) (p = 0.007). Applying LTBI diagnosis guidelines resulted in more psoriasis (50%) than IBD patients (24.2%) receiving treatment for LTBI prior to onset of anti-TNF-α treatment (p = 0.04). In conclusion, current recommendations for LTBI diagnosis must be re-evaluated to account for the unique tuberculin hyperactive state of the skin of patients with psoriasis.