In this study, we investigated the performance of two cuboid scintillation detectors: thallium-activated cesium iodide [CsI(Tl)] and cerium-doped lutetium yttrium orthosilicate [LYSO(Ce)]. The CsI and LYSO crystals were 5 mm thick with an active area of 10 mm × 10 mm. The LYSO scintillator is characterized by its high stopping power and non-hygroscopicity (neither packaging nor light guide are required). Nevertheless, the main disadvantages of LYSO detectors are a lower light output (32 photons/keV) and an intrinsic radioactivity caused by the β decay of Lu (half-life 3.78 × 10 years). In contrast, CsI crystals present a relatively high light output (54 photons/keV) allowing better energy resolution; however, the drawback of a CsI detector is low detection efficiency. First, we measured the photon detection efficiency of each scintillator in the photon energy range of 60-1332 keV using radioactive sources. Second, we computed detector efficiencies using the Monte Carlo codes MCNP and Geant4. A comparison between simulated and measured efficiencies showed a good agreement. This comparison confirmed the validity of the mathematical models developed for the two scintillation detectors CsI(Tl) and LYSO(Ce) under investigation.