In our previous study, we described 26 clinical pneumococci with heterogeneous resistance to telithromycin (TEL). In this study, we investigated the molecular epidemiology of these 26 isolates and compared them to erm(B)-positive but TEL-susceptible (Tels) pneumococci (n=66). Published methods were used for antimicrobial susceptibility testing, serotyping, pulsed-field gel electrophoresis (PFGE) typing, and multilocus sequence typing (MLST). PFGE was performed for all TEL-resistant (Telr) isolates, 3 zone isolates, and 22 randomly selected Tels, erm(B)-positive isolates, while MLST and serotyping were only for Telr isolates, with results compared to international databases. Results showed penicillin nonsusceptibility (MIC ≥0.125 g/ml) was less frequent in erm(B)-positive Telr isolates (4/26) than in Tels isolates (50/66) (P<0.0001). The most frequent serotype was 19A. Telr isolates distributed among 7 PFGE types (type A most frequent with 19 isolates), while Tels isolates had more heterogeneous PFGE patterns. MLST types 193, 271, 273 (representatives of global pneumococcal clones) and new STs (2248, 2306, 2307) were found. The presence of multiple PFGE and MLST types suggests TEL resistance capability arose several times in S. pneumoniae. Resistance was likely not caused by TEL selection pressure as all strains were collected in 2002 (before TEL introduction in Finland). All isolates were of clinical origin, capable of causing human diseases (six from invasive infections). We recommend routine TEL susceptibility testing of pneumococci via disk diffusion in a 5%-CO2 atmosphere, especially in areas where erm(B) is a common resistance mechanism.