We compared an in-house Treponema pallidum IgM immunoblot (IB) with a 19S fluorescent treponemal antibody absorption (IgM) test during routine use for the diagnosis of congenital syphilis (CS) in a national reference laboratory in a nonendemic setting. The overall agreement between the assays was high (97%), and 19S positive samples had at least 2 reactive bands in the IB. The high agreement is mainly caused by the large number of negative results (95%). If the 19S is taken as the gold standard, the estimate sensitivity of the IB was at least 88% with a specificity of 97.2%. Analysis of the discrepancies revealed that the IB was positive with 1 or 2 specific bands in 2.8% of the cases, whereas 19S was negative, possibly indicating higher sensitivity of the IB. We conclude that the IB is a sensitive method to detect contact with T. pallidum in neonates and can replace the 19S in routine laboratory screening for CS cases.