Background: IgM titers of Mycoplasma pneumoniae can remain high for months or years, and specific DNA can be detected in asymptomatic people. Methods: We compared the performance of serology and PCR in children with and without community-acquired pneumonia (CAP) for the diagnosis of M. pneumoniae. Results: In children with CAP, a positive test by M. pneumoniae (PCR and/or paired serology or both) were found in 13.9%. Of these, 10.3% were positive by multiplex PCR (Seeplex-Seegen), and 6.7% exhibited quadrupled titers (22 for IgG, 6 for IgM and 5 for both). Both tests were positive in 2.8% of cases. In the group without CAP, 3.3% were positive by PCR. Thirty-two percent of children with CAP and 38.3% of healthy children had IgM titers >11 in the acute phase. Conclusions: The detection of IgM is not useful for diagnosing acute M. pneumoniae infection, and a positive PCR result can be due to colonization and not infection. New and better diagnostic techniques are required.