Summary In this case series, we retrospectively identified all patients treated with topical sodium thiosulfate (TST) for calcinosis cutis (CC) associated with underlying autoimmune connective tissue diseases at Mayo Clinic (Rochester, MN, USA) during the period 1 January 2012 to 27 June 2017. Of 28 patients identified (mean age 57.0 years; 96% female), 19 (68%) had clinical improvement of their CC with TST, 7 (25%) had no response and 2 (7%) had unknown response. There were adverse events in three patients: two had skin irritation and the third, who had a zinc allergy, experienced pain with application. Overall, our findings support those of previous case reports that TST appears to be a relatively well‐tolerated adjuvant treatment for CC, although future studies with a control group are warranted to assess the true efficacy of TST for the indication of CC.