Laser fluorescence measurements have been shown to be well suited for caries diagnosis. The aim of this study was to compare two laser fluorescence devices and to correlate the respective values with the visual and radiographic assessment and with the extent of the carious lesion. Ninety-four clinically non-cavitated occlusal carious lesions in the premolars and molars of 82 patients were examined. Laser fluorescence values on the surface were measured with a conventional laser fluorescence system and a novel laser fluorescence pen device. When operative intervention at a site was indicated, the extent of caries was determined after its removal. Readings obtained with both systems were significantly different with an interdevice factor of 0.64. Sensitivity and specificity for operative care were 92.6% and 53.7%, respectively, for the conventional, and 88.9% and 53.7%, respectively, for the pen device. For both devices, a correlation between laser fluorescence values and the visual and radiographic assessment and with the extent of the lesion was shown. The study indicates that the novel laser fluorescence device seems to be suitable for occlusal caries diagnosis. However, proposed guidelines for the clinical use of laser fluorescence readings of the conventional device cannot be transferred to the novel pen system.