Telavancin is a dual action, bactericidal lipoglycopeptide. Its in vitro activity was compared with vancomycin and linezolid against 392 Gram-positive isolates from cancer patients. MIC90 values (μg ml(-1)) for telavancin, vancomycin and linezolid were determined for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible (MS), methicillin-resistant (MR), coagulase-negative staphylococci (CoNS), viridans group streptococci (VGS), Streptococcus pneumoniae, Bacillus species, Corynebacterium species and Micrococcus species. Telavancin had potent activity against β-hemolytic streptococci and Staphylococcus lugdunensis. Whereas 100% of MRSA and 98% of MSSA had vancomycin MICs ⩾ 1.0 μg ml(-1) (minimum inhibitory concentrations (MICs) at which poor clinical responses have been reported), the highest telavancin MIC was 0.38 μg ml(-1). For CoNS, 95% of MS and 100% of MR isolates had vancomycin MICs ⩾ 1.0 μg ml(-1), whereas the highest telavancin MIC was 0.38 μg ml(-1). Furthermore, 48% of VGS had vancomycin MICs ⩾ 1.0 μg ml(-1), whereas the highest telavancin MIC was 0.064 μg ml(-1). A similar pattern was noticed for S. lugdunensis, Bacillus species, Corynebacterium species and β-hemolytic streptococci. These data suggest that telavancin and linezolid have potent activity against most Gram-positive organisms that cause infections in cancer patients. Consequently, they may be considered as alternatives to vancomycin, especially in institutions wherein a substantial proportion of infections are caused by organisms with vancomycin MICs ⩾ 1.0 μg ml(-1).