In this paper, Cerium‐doped lutetium yttrium oxyorthosilicate crystal (Lu,Y)2SiO5:Ce (LYSO:Ce) samples were used to thoroughly investigate the structural and optical anisotropy of the crystal. Results presented demonstrate that there is insignificant anisotropy in most of the properties of LYSO:Ce crystal – structural integrity, refractive index, transmittance, excitation and emission spectra, and photoluminescence decay time, which is a comparative advantage for various applications including preparation of optical ceramics. Besides, anisotropy phenomena in fine‐structure of LYSO:Ce, afterglow, thermoluminescence and light output of samples with small size were observed. A mechanism of anisotropy in defect distribution is discussed.