Inclusion Criteria:

* PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
* For pre-surgical patients

* Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology; patients with squamous cell carcinoma are eligible
* Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
* For post-surgical patients

* Completely resected non-small cell lung cancer with negative margins (R0); patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
* Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of AJCC staging will be utilized
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Age ≥ 18 years
* No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
* No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
* No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
* No patients known to be pregnant or lactating
* Patients who have had local genotyping are eligible, regardless of the local result
* No patients with recurrence of lung cancer after prior resection
* Note: Post-surgical patients should proceed to registration immediately following preregistration
* PATIENT REGISTRATION ELIGIBILITY CRITERIA:
* Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
* Completely resected NSCLC with negative margins (R0); cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology
* Pathologic stage IIIA, IIA or IIB, or large IB (defined as size \>= 4 cm); Note: IB tumors \< 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is \>= 4 cm; the 7th edition of AJCC staging will be utilized
* Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
* In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows:

* Squamous patients:

* No adjuvant therapy permitted, register patient within 77 days following surgery
* Non-squamous patients:

* If no adjuvant therapy, register patient within 75 days following surgery
* If adjuvant chemotherapy or radiotherapy only, register patient within 225 days following surgery
* If adjuvant chemotherapy and radiation, register patient within 285 days following surgery