Objectives To evaluate the diagnostic performance of multiple machine learning classifier models derived from first-order histogram texture parameters extracted from T1-weighted contrast-enhanced images in differentiating glioblastoma and primary central nervous system lymphoma. Methods Retrospective study with 97 glioblastoma and 46 primary central nervous system lymphoma patients. Thirty-six different combinations of classifier models and feature selection techniques were evaluated. Five-fold nested cross-validation was performed. Model performance was assessed for whole tumour and largest single slice using receiver operating characteristic curve. Results The cross-validated model performance was relatively similar for the top performing models for both whole tumour and largest single slice (area under the curve 0.909–0.924). However, there was a considerable difference between the worst performing model (logistic regression with full feature set, area under the curve 0.737) and the highest performing model for whole tumour (least absolute shrinkage and selection operator model with correlation filter, area under the curve 0.924). For single slice, the multilayer perceptron model with correlation filter had the highest performance (area under the curve 0.914). No significant difference was seen between the diagnostic performance of the top performing model for both whole tumour and largest single slice. Conclusions T1 contrast-enhanced derived first-order texture analysis can differentiate between glioblastoma and primary central nervous system lymphoma with good diagnostic performance. The machine learning performance can vary significantly depending on the model and feature selection methods. Largest single slice and whole tumour analysis show comparable diagnostic performance.